Toward the Existence of a Sympathetic Neuroplasticity Adaptive Mechanism Influencing the Immune Response. A Hypothetical View-Part II

Emanuel Bottasso, Emanuel Bottasso

Abstract

In the preceding work, a hypothesis on the existence of a specific neural plasticity program from sympathetic fibers innervating secondary lymphoid organs was introduced. This proposed adaptive mechanism would involve segmental retraction and degeneration of noradrenergic terminals during the immune system (IS) activation followed by regeneration once the IS returns to the steady-state. Starting from such view, this second part presents clinical and experimental evidence allowing to envision that this sympathetic neural plasticity mechanism is also operative on inflamed non-lymphoid peripheral tissues. Importantly, the sympathetic nervous system regulates most of the physiological bodily functions, ranging from cardiovascular, respiratory and gastro-intestinal functions to endocrine and metabolic ones, among others. Thus, it seems sensible to think that compensatory programs should be put into place during inflammation in non-lymphoid tissues as well, to avoid the possible detrimental consequences of a sympathetic blockade. Nevertheless, in many pathological scenarios like severe sepsis, chronic inflammatory diseases, or maladaptive immune responses, such compensatory programs against noradrenergic transmission impairment would fail to develop. This would lead to a manifest sympathetic dysfunction in the above-mentioned settings, partly accounting for their underlying pathophysiological basis; which is also discussed. The physiological/teleological significance for the whole neural plasticity process is postulated, as well.

Keywords: inflammation; neural plasticity; neuro-immune interaction; peripheral immune tolerance; sympathetic nervous system.

Copyright © 2019 Bottasso.

Figures

Figure 1
Figure 1
Clinical and experimental evidence of sympathetic structural and functional alterations in many inflammatory scenarios. In different situations in which compensatory mechanisms against sympathetic blockade may be insufficient or may have failed to evolve, sympathetic dysfunction is likely to become evident. This may apply to chronic inflammatory diseases, the ones due to hypersensitivity reactions (maladaptive immune reactions per se), and situations of protracted and dysregulated immune responses failing to eradicate pathogens, i.e., prolonged septicemia. Physiological effects of sympathetic nervous system on different organs are depicted on the left, together with the involved adrenergic-receptor. Evidence suggestive of sympathetic impairment in different pathological conditions is shown on the right. PGP 9.5, protein gene product 9.5; COPD, chronic obstructive pulmonary disease; T1DM, type 1 diabetes mellitus; BDNF, brain-derived neurotrophin factor; p75NTR, p75 neurotrophin receptor; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; NGF, nerve growth factor; AD, atopic dermatitis: NA, norepinephrine. *Mediated by sympathetic adrenergic and non-adrenergic transmission.**Parasympathetic cholinergic neurotransmission elicits in turn bronchoconstriction, increases mucus production and favors airway remodeling (through muscarinic mediated proliferation of bronchial smooth myocytes and fibroblasts). ***Mediated by sympathetic non-adrenergic transmission.

References

    1. Bottasso E. Toward the existence of a sympathetic neuroplasticity adaptive mechanism influencing the immune response. A hypothetical view-part I. Front Endocrinol. (2019) 10:632 10.3389/fendo.2019.00632
    1. Kemi C, Grunewald J, Eklund A, Höglund CO. Differential regulation of neurotrophin expression in human bronchial smooth muscle cells. Respir Res. (2006) 7:18. 10.1186/1465-9921-7-18
    1. Tominaga M, Ogawa H, Takamori K. Decreased production of semaphorin 3A in the lesional skin of atopic dermatitis. Br J Dermatol. (2008) 158:842–4. 10.1111/j.1365-2133.2007.08410.x
    1. Tominaga M, Ozawa S, Ogawa H, Takamori K. A hypothetical mechanism of intraepidermal neurite formation in NC/Nga mice with atopic dermatitis. J Dermatol Sci. (2007) 46:199–210. 10.1016/j.jdermsci.2007.02.002
    1. Tominaga M, Ozawa S, Tengara S, Ogawa H, Takamori K. Intraepidermal nerve fibers increase in dry skin of acetone-treated mice. J Dermatol Sci. (2007) 48:103–11. 10.1016/j.jdermsci.2007.06.003
    1. Kamo A, Tominaga M, Tengara S, Ogawa H, Takamori K. Inhibitory effects of UV-based therapy on dry skin-inducible nerve growth in acetone-treated mice. J Dermatol Sci. (2011) 62:91–7. 10.1016/j.jdermsci.2011.01.004
    1. Jänig W. editor. Functional anatomy of the peripheral sympathetic and parasympathetic system. In: The Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge, UK: Cambridge University Press; (2006). p. 13–34. 10.1017/CBO9780511541667.004
    1. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve–an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. (2000) 52:595–638.
    1. Padro CJ, Sanders VM. Neuroendocrine regulation of inflammation. Semin Immunol. (2014) 26:357–68. 10.1016/j.smim.2014.01.003
    1. Kenney MJ, Ganta CK. Autonomic nervous system and immune system interactions. Compr Physiol. (2014) 4:1177–200. 10.1002/cphy.c130051
    1. Bellinger DL, Lorton D. Sympathetic nerve hyperactivity in the spleen: causal for nonpathogenic-driven chronic Immune-Mediated Inflammatory Diseases (IMIDs)? Int J Mol Sci. (2018) 19:E1188. 10.3390/ijms19041188
    1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. (2016) 315:801–10. 10.1001/jama.2016.0287
    1. Gotts JE, Matthay MA. Sepsis: pathophysiology and clinical management. BMJ. (2016) 353:i1585. 10.1136/bmj.i1585
    1. Gyawali B, Ramakrishna K, Dhamoon AS. Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Med. (2019) 7:2050312119835043. 10.1177/2050312119835043
    1. László I, Trásy D, Molnár Z, Fazakas J. Sepsis: from pathophysiology to individualized patient care. J Immunol Res. (2015) 2015:510436. 10.1155/2015/510436
    1. Sharawy N. Vasoplegia in septic shock: do we really fight the right enemy? J Crit Care. (2014) 29:83–7. 10.1016/j.jcrc.2013.08.021
    1. Kakihana Y, Ito T, Nakahara M, Yamaguchi K, Yasuda T. Sepsis-induced myocardial dysfunction: pathophysiology and management. J Intensive Care. (2016) 4:22. 10.1186/s40560-016-0148-1
    1. Burgdorff AM, Bucher M, Schumann J. Vasoplegia in patients with sepsis and septic shock: pathways and mechanisms. J Int Med Res. (2018) 46:1303–10. 10.1177/0300060517743836
    1. Levy B, Collin S, Sennoun N, Ducrocq N, Kimmoun A, Asfar P, Perez P, et al. . Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med. (2010) 36:2019–29. 10.1007/s00134-010-2045-8
    1. Shaefi S, Mittel A, Klick J, Evans A, Ivascu NS, Gutsche J, et al. . Vasoplegia after cardiovascular procedures-pathophysiology and targeted therapy. J Cardiothorac Vasc Anesth. (2018) 32:1013–22. 10.1053/j.jvca.2017.10.032
    1. Cunnion RE, Parrillo JE. Myocardial dysfunction in sepsis. Crit Care Clin. (1989) 5:99–118. 10.1016/S0749-0704(18)30452-4
    1. Lefer AM, Martin J. Origin of myocardial depressant factor in shock. Am J Physiol. (1970) 218:1423–7. 10.1152/ajplegacy.1970.218.5.1423
    1. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med. (2007) 35:1599–608. 10.1097/01.CCM.0000266683.64081.02
    1. Ly NP, Komatsuzaki K, Fraser IP, Tseng AA, Prodhan P, Moore KJ, et al. . Netrin-1 inhibits leukocyte migration in vitro and in vivo. Proc Natl Acad Sci USA. (2005) 102:14729–34. 10.1073/pnas.0506233102
    1. Rosenberger P, Schwab JM, Mirakaj V, Masekowsky E, Mager A, Morote-Garcia JC, et al. . Hypoxia-inducible factor-dependent induction of netrin-1 dampens inflammation caused by hypoxia. Nat Immunol. (2009) 10:195–202. 10.1038/ni.1683
    1. Borsini A, Zunszain PA, Thuret S, Pariante CM. The role of inflammatory cytokines as key modulators of neurogenesis. Trends Neurosci. (2015) 38:145–57. 10.1016/j.tins.2014.12.006
    1. Poon VY, Choi S, Park M. Growth factors in synaptic function. Front Synaptic Neurosci. (2013) 5:6. 10.3389/fnsyn.2013.00006
    1. Chernogubova E, Cannon B, Bengtsson T. Norepinephrine increases glucose transport in brown adipocytes via β3-adrenoceptors through a cAMP, PKA, and PI3-kinase-dependent pathway stimulating conventional and novel PKCs. Endocrinology. (2004) 145:269–80. 10.1210/en.2003-0857
    1. Cooney GJ, Caterson ID, Newsholme EA. The effect of insulin and noradrenaline on the uptake of 2-[1-14C]deoxyglucose in vivo by brown adipose tissue and other glucose-utilising tissues of the mouse. FEBS Lett. (1985) 188:257–61. 10.1016/0014-5793(85)80383-5
    1. Shimizu Y, Kielar D, Minokoshi Y, Shimazu T. Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin. Biochem J. (1996) 314:485–90. 10.1042/bj3140485
    1. Shimizu Y, Satoh S, Yano H, Minokoshi Y, Cushman SW, Shimazu T. Effects of noradrenaline on the cell-surface glucose transporters in cultured brown adipocytes: novel mechanism for selective activation of GLUT1 glucose transporters. Biochem J. (1998) 330:397–403. 10.1042/bj3300397
    1. Inokuma K, Ogura-Okamatsu Y, Toda C, Kimura K, Yamashita H, Saito M. Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization in brown adipose tissue. Diabetes. (2005) 54:1385–91. 10.2337/diabetes.54.5.1385
    1. Abi-Gerges N, Tavernier B, Mebazaa A, Faivre V, Paqueron X, Payen D, et al. . Sequential changes in autonomic regulation of cardiac myocytes after in vivo endotoxin injection in rat. Am J Respir Crit Care Med. (1999) 160:1196–204. 10.1164/ajrccm.160.4.9808149
    1. Zhong J, Hwang TC, Adams HR, Rubin LJ. Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs. Am J Physiol. (1997) 273:H2312–24. 10.1152/ajpheart.1997.273.5.H2312
    1. Liu S, Schreur KD. G protein-mediated suppression of L-type Ca2+ current by interleukin-1 beta in cultured ratventricular myocytes. Am J Physiol. (1995) 268:C339–49. Erratum in: Am J Physiol. (1995) 268:section C following table of contents. 10.1152/ajpcell.1995.268.2.C339
    1. Schmidt H, Hoyer D, Wilhelm J, Söffker G, Heinroth K, Hottenrott K, et al. . The alteration of autonomic function in multiple organ dysfunction syndrome. Crit Care Clin. (2008) 24:149–63. 10.1016/j.ccc.2007.10.003
    1. Hoyer D, Friedrich H, Zwiener U, Pompe B, Baranowski R, Werdan K, et al. . Prognostic impact of autonomic information in multiple organ dysfunction syndrome patients. Int J Cardiol. (2006) 108:359–69. 10.1016/j.ijcard.2005.05.031
    1. Godin PJ, Buchman TG. Uncoupling of biological oscillators: a complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med. (1996) 24:1107–16. 10.1097/00003246-199607000-00008
    1. Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, et al. . Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med. (1999) 160:458–65. 10.1164/ajrccm.160.2.9810073
    1. Koyoama S, Manning JW. Role of sympathetic nerve activity in endotoxin induced hypotension in cats. Cardiovasc. Res. (1985) 19:32–37. 10.1093/cvr/19.1.32
    1. Sharshar T, Gray F, Lorin de la Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, et al. . Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxidesynthase after death from septic shock. Lancet. (2003) 362:1799–805. 10.1016/S0140-6736(03)14899-4
    1. Corrêa TD, Takala J, Jakob SM. Angiotensin II in septic shock. Crit Care. (2015) 19:98. 10.1186/s13054-015-0802-3
    1. Torpy DJ, Chrousos GP. The three-way interactions between the hypothalamic-pituitary-adrenal and gonadal axes and the immune system. Baillieres Clin Rheumatol. (1996) 10:181–98. 10.1016/S1521-6942(06)80039-2
    1. Silverman MN, Pearce BD, Biron CA, Miller AH. Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol. (2005) 18:41–78. 10.1089/vim.2005.18.41
    1. Polito A, Aboab J, Annane D. Adrenal insufficiency in sepsis. Rev Bras Ter Intensiva. (2006) 18:86–94. 10.1590/S0103-507X2006000100014
    1. Annane D, Bellissant E, Sebille V, Lesieur O, Mathieu B, Raphael JC, et al. . Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve. Br J Clin Pharmacol. (1998) 46:589–97. 10.1046/j.1365-2125.1998.00833.x
    1. Jänig W. editor. The peripheral sympathetic and parasympathetic pathways. In: The Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge, UK: Cambridge University Press; (2006). p. 106–67. 10.1017/CBO9780511541667.007
    1. Kopin IJ. Plasma Levels of Catecholamines and Dopamine-β-Hydroxylase. In: Trendelemburg U, Weiner N, editors. Catecholamines II. Handbook of Experimental Pharmacology, Vol 90/2. Berlin; Heidelberg: Springer; (1989). p. 211–75. 10.1007/978-3-642-73551-6_6
    1. Bocking JK, Sibbald WJ, Holliday RL, Scott S, Viidik T. Plasma catecholamine levels and pulmonary dysfunction in sepsis. Surg Gynecol Obstet. (1979) 148:715–9.
    1. Bernardin G, Strosberg AD, Bernard A, Mattei M, Marullo S. β-adrenergic receptor-dependent and –independent stimulation of adenylate cyclase is impaired during severe sepsis in humans. Intensive Care Med. (1998) 24:1315–22. 10.1007/s001340050768
    1. Hahn PY, Wang P, Tait SM, Ba ZF, Reich SS, Chaudry IH. Sustained elevation in circulating catecholamine levels during polymicrobial sepsis. Shock. (1995) 4:269–73. 10.1097/00024382-199510000-00007
    1. Hwang TL, Lau YT, Huang SF, Chen MF, Liu MS. Changes of α1-adrenergic receptors in human liver during intraabdominal sepsis. Hepatology. (1994) 20:638–42. 10.1002/hep.1840200314
    1. Tang C, Liu MS. Initial externalization followed by internalization of beta-adrenergic receptors in rat heart during sepsis. Am J Physiol. (1996) 270:254–63. 10.1152/ajpregu.1996.270.1.R254
    1. Shepherd RE, Lang CH, McDonough KH. Myocardial adrenergic responsiveness after lethal and nonlethal doses of endotoxin. Am J Physiol. (1987) 252:H410–6. 10.1152/ajpheart.1987.252.2.H410
    1. Reber LL, Hernandez JD, Galli SJ. The pathophysiology of anaphylaxis. J Allergy Clin Immunol. (2017) 140:335–348. 10.1016/j.jaci.2017.06.003
    1. Kemp SF, Lockey RF. Anaphylaxis: a review of causes and mechanisms. J Allergy Clin Immunol. (2002) 110:341–8. 10.1067/mai.2002.126811
    1. Campbell RL, Li JT, Nicklas RA, Sadosty AT; Members of the Joint Task Force; Practice Parameter Workgroup. Emergency department diagnosis and treatment of anaphylaxis: a practice parameter. Ann Allergy Asthma Immunol. (2014) 113:599–608. 10.1016/j.anai.2014.10.007
    1. Ring J, Beyer K, Biedermann T, Bircher A, Duda D, Fischer J, et al. . Guideline for acute therapy and management of anaphylaxis: S2 Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Association of German Allergologists (AeDA), the Society of Pediatric Allergy and Environmental Medicine (GPA), the German Academy of Allergology and Environmental Medicine (DAAU), the German Professional Association of Pediatricians (BVKJ), the Austrian Society for Allergology and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Anaesthesiology and Intensive Care Medicine (DGAI), the German Society of Pharmacology (DGP), the German Society for Psychosomatic Medicine (DGPM), the German Working Group of Anaphylaxis Training and Education (AGATE) and the patient organization German Allergy and Asthma Association (DAAB). Allergo J Int. (2014) 23:96–112. 10.1007/s40629-014-0009-1
    1. Leon A, Buriani A, Dal Toso R, Fabris M, Romanello S, Aloe L, et al. . Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci USA. (1994) 91:3739–43. 10.1073/pnas.91.9.3739
    1. Casha S, Christie S. A systematic review of intensive cardiopulmonary management after spinal cord injury. J Neurotrauma. (2011) 28:1479–95. 10.1089/neu.2009.1156
    1. Popa C, Popa F, Grigorean VT, Onose G, Sandu AM, Popescu M, et al. . Vascular dysfunctions following spinal cord injury. J Med Life. (2010) 3:275–85.
    1. Partida E, Mironets E, Hou S, Tom VJ. Cardiovascular dysfunction following spinal cord injury. Neural Regen Res. (2016) 11:189–94. 10.4103/1673-5374.177707
    1. Mitchell RN, Schoen FJ. Blood Vessels. In: Kumar V, Abbas AK, Aster JC. editors. Robbins Basic Pathology. Philadelphia, PA: Elsevier Saunders; (2018). p. 361–98.
    1. Golledge J. Abdominal aortic aneurysm: update on pathogenesis and medical treatments. Nat Rev Cardiol. (2019) 16:225–42. 10.1038/s41569-018-0114-9
    1. Nordon IM, Hinchliffe RJ, Loftus IM, Thompson MM. Pathophysiology and epidemiology of abdominal aortic aneurysms. Nat Rev Cardiol. (2011) 8:92–102. 10.1038/nrcardio.2010.180
    1. Li H, Bai S, Ao Q, Wang X, Tian X, Li X, et al. . Modulation of immune-inflammatory responses in abdominal aortic aneurysm: emerging molecular targets. J Immunol Res. (2018) 2018:7213760. 10.1155/2018/7213760
    1. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol. (2009) 27:165–97. 10.1146/annurev.immunol.021908.132620
    1. Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. (2012) 32:2045–51. 10.1161/ATVBAHA.108.179705
    1. Fredman G, Tabas I. Boosting inflammation resolution in atherosclerosis: the next frontier for therapy. Am J Pathol. (2017) 187:1211–21. 10.1016/j.ajpath.2017.01.018
    1. Hellenthal FA, Geenen IL, Teijink JA, Heeneman S, Schurink GW. Histological features of human abdominal aortic aneurysm are not related to clinical characteristics. Cardiovasc Pathol. (2009) 18:286–93. 10.1016/j.carpath.2008.06.014
    1. Rodella LF, Rezzani R, Bonomini F, Peroni M, Cocchi MA, Hirtler L, et al. . Abdominal aortic aneurysm and histological, clinical, radiological correlation. Acta Histochem. (2016) 118:256–62. 10.1016/j.acthis.2016.01.007
    1. Paulo N, Cascarejo J, Vouga L. Syphilitic aneurysm of the ascending aorta. Interact Cardiovasc Thorac Surg. (2012) 14:223–5. 10.1093/icvts/ivr067
    1. Roberts WC, Barbin CM, Weissenborn MR, Ko JM, Henry AC. Syphilis as a cause of thoracic aortic aneurysm. Am J Cardiol. (2015) 116:1298–303. 10.1016/j.amjcard.2015.07.030
    1. Brown SL, Busuttil RW, Baker JD, Machleder HI, Moore WS, Barker WF. Bacteriologic and surgical determinants of survival in patients with mycotic aneurysms. J Vasc Surg. (1984) 1:541–7. 10.1016/0741-5214(84)90040-5
    1. Lee WK, Mossop PJ, Little AF, Fitt GJ, Vrazas JI, Hoang JK, et al. . Infected (mycotic) aneurysms: spectrum of imaging appearances and management. Radiographics. (2008) 28:1853–68. 10.1148/rg.287085054
    1. Bevan RD. Effect of sympathetic denervation on smooth muscle cell proliferation in the growing rabbit ear artery. Circ Res. (1975) 37:14–9. 10.1161/01.RES.37.1.14
    1. Chamley JH, Campbell GR. Trophic influences of sympathetic nerves and cyclic AMP on differentiation and proliferation of isolated smooth muscle cells in culture. Cell Tissue Res. (1975) 161:497–510. 10.1007/BF00224140
    1. Fronek K. Trophic effect of the sympathetic nervous system on vascular smooth muscle. Ann Biomed Eng. (1983) 11:607–15. 10.1007/BF02364090
    1. Erlinge D, Yoo H, Edvinsson L, Reis DJ, Wahlestedt C. Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters. Am J Physiol. (1993) 265:H1089–97. 10.1152/ajpheart.1993.265.4.H1089
    1. Erlinge D, Brunkwall J, Edvinsson L. Neuropeptide Y stimulates proliferation of human vascular smooth muscle cells: cooperation with noradrenaline and ATP. Regul Pept. (1994) 50:259–65. 10.1016/0167-0115(94)90006-X
    1. Zhang H, Faber JE. Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different alpha1-adrenoceptor subtypes. Circ Res. (2001) 89:815–22. 10.1161/hh2101.098379
    1. Dechant G, Barde YA. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci. (2002) 5:1131–6. 10.1038/nn1102-1131
    1. Kenchappa RS, Tep C, Korade Z, Urra S, Bronfman FC, Yoon SO, et al. . p75 neurotrophin receptor-mediated apoptosis in sympathetic neurons involves a biphasic activation of JNK and up-regulation of tumor necrosis factor-alpha-converting enzyme/ADAM17. J Biol Chem. (2010) 285:20358–68. 10.1074/jbc.M109.082834
    1. Kraemer BR, Snow JP, Vollbrecht P, Pathak A, Valentine WM, Deutch AY, et al. . A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis induced by oxidative stress. J Biol Chem. (2014) 289:21205–16. 10.1074/jbc.M114.563403
    1. Bush A. Pathophysiological mechanisms of asthma. Front Pediatr. (2019) 7:68. 10.3389/fped.2019.00068
    1. Olin JT, Wechsler ME. Asthma: pathogenesis and novel drugs for treatment. BMJ. (2014) 349:g5517. 10.1136/bmj.g5517
    1. McCracken JL, Veeranki SP, Ameredes BT, Calhoun WJ. Diagnosis and management of asthma in adults: a review. JAMA. (2017) 318:279–90. 10.1001/jama.2017.8372
    1. Schatz M, Rosenwasser L. The allergic asthma phenotype. J Allergy Clin Immunol Pract. (2014) 2:645–8; quiz 649. 10.1016/j.jaip.2014.09.004
    1. Peters SP. Asthma phenotypes: nonallergic (intrinsic) asthma. J Allergy Clin Immunol Pract. (2014) 2:650–2. 10.1016/j.jaip.2014.09.006
    1. Szentivanyi A. The beta-adrenergic theory of the atopic abnormality in bronchial asthma. J Allergy Clin Immunol. (1968) 42:203–32. 10.1016/S0021-8707(68)90117-2
    1. Lemanske RF, Jr, Kaliner MA. Autonomic nervous system abnormalities and asthma. Am Rev Respir Dis. (1990) 141:S157–61. 10.1164/ajrccm/141.3_Pt_2.S157
    1. Jartti T. Asthma, asthma medication and autonomic nervous system dysfunction. Clin Physiol. (2001) 21:260–9. 10.1046/j.1365-2281.2001.00323.x
    1. Mazzone SB, Undem BJ. Vagal afferent innervation of the airways in health and disease. Physiol Rev. (2016) 96:975–1024. 10.1152/physrev.00039.2015
    1. Undem BJ, Carr MJ. The role of nerves in asthma. Curr Allergy Asthma Rep. (2002) 2:159–65. 10.1007/s11882-002-0011-4
    1. van der Velden VH, Hulsmann AR. Autonomic innervation of human airways: structure, function, and pathophysiology in asthma. Neuroimmunomodulation. (1999) 6:145–59. 10.1159/000026376
    1. de Jongste JC, Jongejan RC, Kerrebijn KF. Control of airway caliber by autonomic nerves in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis. (1991) 143:1421–6. 10.1164/ajrccm/143.6.1421
    1. Grundstrom N, Andersson ROO. Inhibition of the cholinergic neurotransmission in human airways via prejunctional alpha-2-adrenoceptors. Acta Physiol Scand. (1985) 125:513–7. 10.1111/j.1748-1716.1985.tb07749.x
    1. Davis C, Kannan MS. Sympathetic innervations of human tracheal and bronchial smooth muscle. Respir Physiol. (1987) 68:53–61. 10.1016/0034-5687(87)90076-4
    1. Morales DR, Dreischulte T, Lipworth BJ, Donnan PT, Jackson C, Guthrie B. Respiratory effect of beta-blocker eye drops in asthma: population-based study and meta-analysis of clinical trials. Br J Clin Pharmacol. (2016) 82:814–22. 10.1111/bcp.13006
    1. Morales DR, Jackson C, Lipworth BJ, Donnan PT, Guthrie B. Adverse respiratory effect of acute β-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials. Chest. (2014) 145:779–786. 10.1378/chest.13-1235
    1. Empey DW, Laitinen LA, Jacobs L, Gold WM, Nadel JA. Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Am Rev Respir Dis. (1976) 113:131–9.
    1. Laitinen LA, Elkin RB, Empey DW, Jacobs L, Mills J, Nadel JA. Bronchial hyperresponsiveness in normal subjects during attenuated influenza virus infection. Am Rev Respir Dis. (1991) 143:358–61. 10.1164/ajrccm/143.2.358
    1. Freymuth F, Vabret A, Gouarin S, Petitjean J, Campet M: [Epidemiology of respiratory virus infections] Allerg Immunol. (2001) 33:66–9.
    1. Pérez-Yarza EG, Moreno A, Lázaro P, Mejías A, Ramilo O. The association between respiratory syncytial virus infection and the development of childhood asthma: a systematic review of the literature. Pediatr Infect Dis J. (2007) 26:733–9. 10.1097/INF.0b013e3180618c42
    1. Fjaerli HO, Farstad T, Rød G, Ufert GK, Gulbrandsen P, Nakstad B. Acute bronchiolitis in infancy as risk factor for wheezing and reduced pulmonary function by seven years in Akershus County, Norway. BMC Pediatr. (2005) 5:31. 10.1186/1471-2431-5-31
    1. Mirza S, Clay RD, Koslow MA, Scanlon PD. COPD Guidelines: a review of the 2018 GOLD Report. Mayo Clin Proc. (2018) 93:1488–502. 10.1016/j.mayocp.2018.05.026
    1. Rossi A, Butorac-Petanjek B, Chilosi M, Cosío BG, Flezar M, Koulouris N, et al. . Chronic obstructive pulmonary disease with mild airflow limitation: current knowledge and proposal for future research - a consensus document from six scientific societies. Int J Chron Obstruct Pulmon Dis. (2017) 12:2593–610. 10.2147/COPD.S132236
    1. GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. (2017) 5:691–706. 10.1016/S2213-2600(17)30293-X
    1. Papaiwannou A, Zarogoulidis P, Porpodis K, Spyratos D, Kioumis I, Pitsiou G, et al. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current literature review. J Thorac Dis. (2014) 6 Suppl 1:S146–51. 10.3978/j.issn.2072-1439.2014.03.04
    1. Brown PJ, Greville HW, Finucane KE. Asthma and irreversible airflow obstruction. Thorax. (1984) 39:131–6. 10.1136/thx.39.2.131
    1. Backman KS, Greenberger PA, Patterson R. Airways obstruction in patients with long-term asthma consistent with irreversible asthma. Chest. (1997) 112:1234–40. 10.1378/chest.112.5.1234
    1. Vonk JM, Jongepier H, Panhuysen CIM, Schouten JP, Bleecker ER, Postma DS. Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up. Thorax. (2003) 58:322–7. 10.1136/thorax.58.4.322
    1. Grzela K, Litwiniuk M, Zagorska W, Grzela T. Airway remodeling in chronic obstructive pulmonary disease and asthma: the role of matrix metalloproteinase-9. Arch Immunol Ther Exp (Warsz). (2016) 64:47–55. 10.1007/s00005-015-0345-y
    1. Lambert RK, Wiggs BR, Kuwano K, Hogg JC, Paré PD. Functional significance of increased airway smooth muscle in asthma and COPD. J Appl Physiol. (1993) 74:2771–81. 10.1152/jappl.1993.74.6.2771
    1. Meurs H, Dekkers BG, Maarsingh H, Halayko AJ, Zaagsma J, Gosens R. Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target. Pulm Pharmacol Ther. (2013) 26:145–55. 10.1016/j.pupt.2012.07.003
    1. Kistemaker LE, Oenema TA, Meurs H, Gosens R. Regulation of airway inflammation and remodeling by muscarinic receptors: perspectives on anticholinergic therapy in asthma and COPD. Life Sci. (2012) 91:1126–33. 10.1016/j.lfs.2012.02.021
    1. Koarai A, Ichinose M. Possible involvement of acetylcholine-mediated inflammation in airway diseases. Allergol Int. (2018) 67:460–6. 10.1016/j.alit.2018.02.008
    1. Gosens R, Gross N. The mode of action of anticholinergics in asthma. Eur Respir J. (2018) 52:1701247. 10.1183/13993003.01247-2017
    1. DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers. (2015) 1:15019 10.1038/nrdp.2015.39
    1. Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. . Type 1 diabetes mellitus. Nat Rev Dis Primers. (2017) 3:17016. 10.1038/nrdp.2017.16
    1. Krogvold L, Wiberg A, Edwin B, Buanes T, Jahnsen FL, Hanssen KF, et al. . Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes. Diabetologia. (2016) 59:492–501. 10.1007/s00125-015-3820-4
    1. Krogvold L, Edwin B, Buanes T, Ludvigsson J, Korsgren O, Hyöty H, et al. . Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study. Diabetologia. (2014) 57:841–3. 10.1007/s00125-013-3155-y
    1. Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K, et al. . Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes: close correlation between serological markers and histological evidence of cellular autoimmunity. Diabetes. (2001) 50:1269–73. 10.2337/diabetes.50.6.1269
    1. Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. (1985) 313:353–60. 10.1056/NEJM198508083130604
    1. Ahrén B. Autonomic regulation of islet hormone secretion–implications for health and disease. Diabetologia. (2000) 43:393–410. 10.1007/s001250051322
    1. Taborsky GJ, Jr. The physiology of glucagon. J Diabetes Sci Technol. (2010) 4:1338–44. 10.1177/193229681000400607
    1. Taborsky GJ, Jr, Mundinger TO. The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia. Endocrinology. (2012) 153:1055–62. 10.1210/en.2011-2040
    1. Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science. (1973) 182:171–3. 10.1126/science.182.4108.171
    1. Mundinger TO, Taborsky GJ, Jr. Early sympathetic islet neuropathy in autoimmune diabetes: lessons learned and opportunities for investigation. Diabetologia. (2016) 59:2058–67. 10.1007/s00125-016-4026-0
    1. Mei Q, Mundinger TO, Lernmark A, Taborsky GJ, Jr. Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats. Diabetes. (2002) 51:2997–3002. Erratum in: Diabetes. (2002) 51: 3591. 10.2337/diabetes.51.10.2997
    1. Taborsky GJ, Jr, Mei Q, Hackney DJ, Figlewicz DP, LeBoeuf R, Mundinger TO. Loss of islet sympathetic nerves and impairment of glucagon secretion in the NOD mouse: relationship to invasive insulitis. Diabetologia. (2009) 52:2602–11. 10.1007/s00125-009-1494-5
    1. Taborsky GJ, Jr, Mei Q, Bornfeldt KE, Hackney DJ, Mundinger TO. The p75 neurotrophin receptor is required for the major loss of sympathetic nerves from islets under autoimmune attack. Diabetes. (2014) 63:2369–79. 10.2337/db13-0778
    1. Mundinger TO, Mei Q, Foulis AK, Fligner CL, Hull RL, Taborsky GJ, Jr. Human Type 1 diabetes is characterized by an early, marked, sustained, and islet-selective loss of sympathetic nerves. Diabetes. (2016) 65:2322–30. 10.2337/db16-0284
    1. Taborsky GJ, Jr, Mei Q, Hackney DJ, Mundinger TO. The search for the mechanism of early sympathetic islet neuropathy in autoimmune diabetes. Diabetes Obes Metab. (2014) 16(Suppl. 1):96–101. 10.1111/dom.12341
    1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. . Heart disease and stroke statistics−2015 update: a report from the American Heart Association. Circulation. (2015) 131:e29–322. 10.1161/CIR.0000000000000152
    1. Francis Stuart SD, De Jesus NM, Lindsey ML, Ripplinger CM. The crossroads of inflammation, fibrosis, and arrhythmia following myocardial infarction. J Mol Cell Cardiol. (2016) 91:114–22. 10.1016/j.yjmcc.2015.12.024
    1. Ong SB, Hernández-Reséndiz S, Crespo-Avilan GE, Mukhametshina RT, Kwek XY, Cabrera-Fuentes HA, et al. . Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacol Ther. (2018) 186:73–87. 10.1016/j.pharmthera.2018.01.001
    1. Parrish DC, Francis Stuart SD, Olivas A, Wang L, Nykjaer A, Ripplinger CM, et al. Transient denervation of viable myocardium after myocardial infarction does not alter arrhythmia susceptibility. Am J Physiol Heart Circ Physiol. (2018) 314:H415–23. 10.1152/ajpheart.00300.2017
    1. Stanton MS, Tuli MM, Radtke NL, Heger JJ, Miles WM, Mock BH, et al. . Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine. J Am Coll Cardiol. (1989) 14:1519–26. 10.1016/0735-1097(89)90391-4
    1. Kammerling JJ, Green FJ, Watanabe AM, Inoue H, Barber MJ, Henry DP, et al. . Denervation supersensitivity of refractoriness in noninfarcted areas apical to transmural myocardial infarction. Circulation. (1987) 76:383–93. 10.1161/01.CIR.76.2.383
    1. Li W, Knowlton D, Van Winkle DM, Habecker BA. Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons. Am J Physiol Heart Circ Physiol. (2004) 286:H2229–36. 10.1152/ajpheart.00768.2003
    1. Hiltunen JO, Laurikainen A, Väkevä A, Meri S, Saarma M. Nerve growth factor and brain-derived neurotrophic factor mRNAs are regulated in distinct cell populations of rat heart after ischaemia and reperfusion. J Pathol. (2001) 194:247–53. 10.1002/path.878
    1. Lorentz CU, Parrish DC, Alston EN, Pellegrino MJ, Woodward WR, Hempstead BL, et al. . Sympathetic denervation of peri-infarct myocardium requires the p75 neurotrophin receptor. Exp Neurol. (2013) 249:111–9. 10.1016/j.expneurol.2013.08.015
    1. Boogers MJ, Borleffs CJ, Henneman MM, van Bommel RJ, van Ramshorst J, Boersma E, et al. . Cardiac sympathetic denervation assessed with 123-iodine metaiodobenzylguanidine imaging predicts ventricular arrhythmias in implantable cardioverter-defibrillator patients. J Am Coll Cardiol. (2010) 55:2769–77. 10.1016/j.jacc.2009.12.066
    1. Fallavollita JA, Heavey BM, Luisi AJ, Jr, Michalek SM, Baldwa S, Mashtare TL, Jr, et al. . Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy. J Am Coll Cardiol. (2014) 63:141–9. 10.1016/j.jacc.2013.07.096
    1. Nishisato K, Hashimoto A, Nakata T, Doi T, Yamamoto H, Nagahara D, et al. . Impaired cardiac sympathetic innervation and myocardial perfusion are related to lethal arrhythmia: quantification of cardiac tracers in patients with ICDs. J Nucl Med. (2010) 51:1241–9. 10.2967/jnumed.110.074971
    1. Tominaga M, Takamori K. Recent advances in pathophysiological mechanisms of itch. Expert Rev Dermatol. (2010) 5:197–212. 10.1586/edm.10.7
    1. Tominaga M, Takamori K. Itch and nerve fibers with special reference to atopic dermatitis: therapeutic implications. J Dermatol. (2014) 41:205–12. 10.1111/1346-8138.12317
    1. Tominaga M, Ogawa H, Takamori K. Histological characterization of cutaneous nerve fibers containing gastrin-releasing peptide in NC/Nga mice: an atopic dermatitis model. J Invest Dermatol. (2009) 129:2901–5. 10.1038/jid.2009.188
    1. Takaoka K, Shirai Y, Saito N. Inflammatory cytokine tumor necrosis factor-alpha enhances nerve growth factor production in human keratinocytes, HaCaT cells. J Pharmacol Sci. (2009) 111:381–91. 10.1254/jphs.09143FP
    1. Kakurai M, Monteforte R, Suto H, Tsai M, Nakae S, Galli SJ. Mast cell-derived tumor necrosis factor can promote nerve fiber elongation in the skin during contact hypersensitivity in mice. Am J Pathol. (2006) 169:1713–21. 10.2353/ajpath.2006.060602
    1. Tobin D, Nabarro G, Baart de la Faille H, van Vloten WA, van der Putte SC, Schuurman HJ. Increased number of immunoreactive nerve fibers in atopic dermatitis. J Allergy Clin Immunol. (1992) 90:613–22. 10.1016/0091-6749(92)90134-N
    1. Cicek D, Kandi B, Berilgen MS, Bulut S, Tekatas A, Dertlioglu SB, et al. . Does autonomic dysfunction play a role in atopic dermatitis? Br J Dermatol. (2008) 159:834–8. 10.1111/j.1365-2133.2008.08756.x
    1. Haligür BD, Cicek D, Bulut S, Berilgen MS. The investigation of autonomic functions in patients with psoriasis. Int J Dermatol. (2012) 51:557–63. 10.1111/j.1365-4632.2011.05111.x
    1. Stead RH, Kosecka-Janiszewska U, Oestreicher AB, Dixon MF, Bienenstock J. Remodeling of B-50 (GAP-43)- and NSE-immunoreactive mucosal nerves in the intestines of rats infected with Nippostrongylus brasiliensis. J Neurosci. (1991) 11:3809–21. 10.1523/JNEUROSCI.11-12-03809.1991
    1. Stead RH. Nerve remodelling during intestinal inflammation. Ann N Y Acad Sci. (1992) 664:443–55. 10.1111/j.1749-6632.1992.tb39782.x
    1. Swain MG, Blennerhassett PA, Collins SM. Impaired sympathetic nerve function in the inflamed rat intestine. Gastroenterology. (1991) 100:675–82. 10.1016/0016-5085(91)80011-W
    1. Boissé L, Chisholm SP, Lukewich MK, Lomax AE. Clinical and experimental evidence of sympathetic neural dysfunction during inflammatory bowel disease. Clin Exp Pharmacol Physiol. (2009) 36:1026–33. 10.1111/j.1440-1681.2009.05242.x
    1. Motagally MA, Neshat S, Lomax AE. Inhibition of sympathetic N-type voltage-gated Ca2+ current underlies the reduction in norepinephrine release during colitis. Am J Physiol Gastrointest Liver Physiol. (2009) 296:G1077–84. 10.1152/ajpgi.00006.2009
    1. Jänig W. editor. The enteric nervous system. In: The Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge, UK: Cambridge University Press; (2006). p. 168–207. 10.1017/CBO9780511541667
    1. Lomax AE, Sharkey KA, Furness JB. The participation of the sympathetic innervation of the gastrointestinal tract in disease states. Neurogastroenterol Motil. (2010) 22:7–18. 10.1111/j.1365-2982.2009.01381.x
    1. Brierley SM, Linden DR. Neuroplasticity and dysfunction after gastrointestinal inflammation. Nat Rev Gastroenterol Hepatol. (2014) 11:611–27. 10.1038/nrgastro.2014.103
    1. Moynes DM, Lucas GH, Beyak MJ, Lomax AE. Effects of inflammation on the innervation of the colon. Toxicol Pathol. (2014) 42:111–7. 10.1177/0192623313505929
    1. Lomax AE, Pradhananga S, Bertrand PP. Plasticity of neuroeffector transmission during bowel inflammation1. Am J Physiol Gastrointest Liver Physiol. (2017) 312:G165–70. 10.1152/ajpgi.00365.2016
    1. Weidler C, Holzer C, Harbuz M, Hofbauer R, Angele P, Schölmerich J, et al. . Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium. Ann Rheum Dis. (2005) 64:13–20. 10.1136/ard.2003.016154
    1. Miller LE, Weidler C, Falk W, Angele P, Schaumburger J, Schölmerich J, et al. . Increased prevalence of semaphorin 3C, a repellent of sympathetic nerve fibers, in the synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum. (2004) 50:1156–63. 10.1002/art.20110
    1. Petersen LE, Baptista TSA, Molina JK, Motta JG, do Prado A, Piovesan DM, et al. . Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets, cytokines and neurotrophic factors. Clin Rheumatol. (2018) 37:1171–81. 10.1007/s10067-018-3990-9
    1. del Rey A, Wolff C, Wildmann J, Randolf A, Hahnel A, Besedovsky HO, et al. . Disrupted brain-immune system-joint communication during experimental arthritis. Arthritis Rheum. (2008) 58:3090–9. 10.1002/art.23869
    1. del Rey A, Wolff C, Wildmann J, Randolf A, Straub RH, Besedovsky HO. When immune-neuro-endocrine interactions are disrupted: experimentally induced arthritis as an example. Neuroimmunomodulation. (2010) 17:165–8. 10.1159/000258714
    1. Wolff C, Straub RH, Hahnel A, Randolf A, Wildmann J, Besedovsky HO, et al. . Mimicking disruption of brain-immune system-joint communication results in collagen type II-induced arthritis in non-susceptible PVG rats. Mol Cell Endocrinol. (2015) 415:56–63. 10.1016/j.mce.2015.08.005
    1. Levick JR. Microvascular architecture and exchange in synovial joints. Microcirculation. (1995) 2:217–33. 10.3109/10739689509146768
    1. Ferrell WR, Khoshbaten A. Responses of blood vessels in the rabbit knee to electrical stimulation of the joint capsule. J Physiol. (1990) 423:569–78. 10.1113/jphysiol.1990.sp018040
    1. Pereira PC, Navarro EC. Challenges and perspectives of Chagas disease: a review. J Venom Anim Toxins Incl Trop Dis. (2013) 19:34. 10.1186/1678-9199-19-34
    1. Malik LH, Singh GD, Amsterdam EA. Chagas heart disease: an update. Am J Med. (2015) 128:1251.e7–9. 10.1016/j.amjmed.2015.04.036
    1. Lidani KCF, Andrade FA, Bavia L, Damasceno FS, Beltrame MH, Messias-Reason IJ, et al. . Chagas disease: from discovery to a worldwide health problem. Front Public Health. (2019) 7:166. 10.3389/fpubh.2019.00166
    1. Meneghelli UG. Chagas' disease: a model of denervation in the study of digestive tract motility. Braz J Med Biol Res. (1985) 18:255–64.
    1. Pérez-Molina JA, Molina I. Chagas disease. Lancet. (2018) 391:82–94. 10.1016/S0140-6736(17)31612-4
    1. Chavan SS, Tracey KJ. Essential neuroscience in immunology. J Immunol. (2017) 198:3389–97. 10.4049/jimmunol.1601613
    1. Pavlov VA, Chavan SS, Tracey KJ. Molecular and functional neuroscience in immunity. Annu Rev Immunol. (2018) 36:783–812. 10.1146/annurev-immunol-042617-053158
    1. McMahon SB, La Russa F, Bennett DL. Crosstalk between the nociceptive and immune systems in host defence and disease. Nat Rev Neurosci. (2015) 16:389–402. 10.1038/nrn3946
    1. Pinho-Ribeiro FA, Verri WA, Jr, Chiu IM. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol. (2017) 38:5–19. 10.1016/j.it.2016.10.001
    1. Pearse AG. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. (1969) 17:303–13. 10.1177/17.5.303
    1. Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 9th ed. Philadelphia, PA: Saunders Elsevier; (2017).
    1. Herman A, Kappler JW, Marrack P, Pullen AM. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol. (1991) 9:745–72. 10.1146/annurev.iy.09.040191.003525
    1. MacDonald HR, Lees RK, Baschieri S, Herrmann T, Lussow AR. Peripheral T-cell reactivity to bacterial superantigens in vivo: the response/anergy paradox. Immunol Rev. (1993) 133:105–17. 10.1111/j.1600-065X.1993.tb01512.x
    1. del Rey A, Kabiersch A, Petzoldt S, Randolf A, Besedovsky HO. Sympathetic innervation affects superantigen-induced decrease in CD4V beta 8 cells in the spleen. Ann N Y Acad Sci. (2000) 917:575–81. 10.1111/j.1749-6632.2000.tb05423.x
    1. del Rey A, Kabiersch A, Petzoldt S, Besedovsky HO. Involvement of noradrenergic nerves in the activation and clonal deletion of T cells stimulated by superantigen in vivo. J Neuroimmunol. (2002) 127:44–53. 10.1016/S0165-5728(02)00096-6
    1. Alaniz RC, Thomas SA, Perez-Melgosa M, Mueller K, Farr AG, Palmiter RD, et al. . Dopamine beta-hydroxylase deficiency impairs cellular immunity. Proc Natl Acad Sci USA. (1999) 96:2274–8. 10.1073/pnas.96.5.2274
    1. Barrios-Payán J, Revuelta A, Mata-Espinosa D, Marquina-Castillo B, Villanueva EB, Gutiérrez ME, et al. . The contribution of the sympathetic nervous system to the immunopathology of experimental pulmonary tuberculosis. J Neuroimmunol. (2016) 298:98–105. 10.1016/j.jneuroim.2016.07.012
    1. Pacheco-López G, Niemi MB, Kou W, Bildhäuser A, Gross CM, Goebel MU, et al. . Central catecholamine depletion inhibits peripheral lymphocyte responsiveness in spleen and blood. J Neurochem. (2003) 86:1024–31. 10.1046/j.1471-4159.2003.01914.x
    1. Filipov NM, Cao L, Seegal RF, Lawrence DA. Compromised peripheral immunity of mice injected intrastriatally with six-hydroxydopamine. J Neuroimmunol. (2002) 132:129–39. 10.1016/S0165-5728(02)00321-1
    1. ThyagaRajan S, Madden KS, Teruya B, Stevens SY, Felten DL, Bellinger DL. Age-associated alterations in sympathetic noradrenergic innervation of primary and secondary lymphoid organs in female Fischer 344 rats. J Neuroimmunol. (2011) 233:54–64. 10.1016/j.jneuroim.2010.11.012
    1. Wirth T, Westendorf AM, Bloemker D, Wildmann J, Engler H, Mollerus S, et al. . The sympathetic nervous system modulates CD4+Foxp3+ regulatory T cells via noradrenaline-dependent apoptosis in a murine model of lymphoproliferative disease. Brain Behav Immun. (2014) 38:100–10. 10.1016/j.bbi.2014.01.007
    1. Bhowmick S, Singh A, Flavell RA, Clark RB, O'Rourke J, Cone RE. The sympathetic nervous system modulates CD4+FoxP3+ regulatory T cells via a TGF-β-dependent mechanism. J Leukoc Biol. (2009) 86:1275–83. 10.1189/jlb.0209107
    1. Prass K, Meisel C, Höflich C, Braun J, Halle E, Wolf T, et al. . Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. (2003) 198:725–36. 10.1084/jem.20021098
    1. Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. (2005) 6:775–86. 10.1038/nrn1765
    1. Prass K, Braun JS, Dirnagl U, Meisel C, Meisel A. Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia. Stroke. (2006) 37:2607–12. 10.1161/01.STR.0000240409.68739.2b
    1. Walter U, Kolbaske S, Patejdl R, Steinhagen V, Abu-Mugheisib M, Grossmann A, et al. . Insular stroke is associated with acute sympathetic hyperactivation and immunodepression. Eur J Neurol. (2013) 20:153–9. 10.1111/j.1468-1331.2012.03818.x
    1. Winklewski PJ, Radkowski M, Demkow U. Cross-talk between the inflammatory response, sympathetic activation and pulmonary infection in the ischemic stroke. J Neuroinflammation. (2014) 11:213. 10.1186/s12974-014-0213-4
    1. Allison DJ, Ditor DS. Immune dysfunction and chronic inflammation following spinal cord injury. Spinal Cord. (2015) 53:14–8. 10.1038/sc.2014.184
    1. Tibbs PA, Young B, Ziegler MG, McAllister RG., Jr Studies of experimental cervical spinal cord transection. Part II: Plasma norepinephrine levels after acute cervical spinal cord transection. J Neurosurg. (1979) 50:629–32. 10.3171/jns.1979.50.5.0629
    1. Reiche EM, Nunes SO, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol. (2004) 5:617–25. 10.1016/S1470-2045(04)01597-9
    1. Veith RC, Lewis N, Linares OA, Barnes RF, Raskind MA, Villacres EC, et al. . Sympathetic nervous system activity in major depression. Basal and desipramine-induced alterations in plasma norepinephrine kinetics. Arch Gen Psychiatry. (1994) 51:411–22. 10.1001/archpsyc.1994.03950050071008
    1. Hernandez ME, Martinez-Mota L, Salinas C, Marquez-Velasco R, Hernandez-Chan NG, Morales-Montor J, et al. . Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats. Biomed Res Int. (2013) 2013:868742. 10.1155/2013/868742
    1. Thompson M, Bywaters EG. Unilateral rheumatoid arthritis following hemiplegia. Ann Rheum Dis. (1962) 21:370–7. 10.1136/ard.21.4.370
    1. Sethi S, Sequeira W. Sparing effect of hemiplegia on scleroderma. Ann Rheum Dis. (1990) 49:999–1000. 10.1136/ard.49.12.999
    1. Veale D, Farrell M, Fitzgerald O. Mechanism of joint sparing in a patient with unilateral psoriatic arthritis and a longstanding hemiplegia. Br J Rheumatol. (1993) 32:413–6. 10.1093/rheumatology/32.5.413
    1. Dolan AL. Asymmetric rheumatoid vasculitis in a hemiplegic patient. Ann Rheum Dis. (1995) 54:532. 10.1136/ard.54.6.532
    1. Lapadula G, Iannone F, Zuccaro C, Covelli M, Grattagliano V, Pipitone V. Recovery of erosive rheumatoid arthritis after human immunodeficiency virus-1 infection and hemiplegia. J Rheumatol. (1997) 24:747–51.
    1. Herfort RA. Extended sympathectomy in the treatment of advanced rheumatoid arthritis; a preliminary report. N Y State J Med. (1956) 56:1292–4.
    1. Tarkowski E, Naver H, Wallin BG, Blomstrand C, Tarkowski A. Lateralization of T-lymphocyte responses in patients with stroke. Effect of sympathetic dysfunction? Stroke. (1995) 26:57–62. 10.1161/01.STR.26.1.57
    1. Aloe L, Tuveri MA, Levi-Montalcini R. Studies on carrageenan-induced arthritis in adult rats: presence of nerve growth factor and role of sympathetic innervation. Rheumatol Int. (1992) 12:213–6. 10.1007/BF00302155
    1. Härle P, Möbius D, Carr DJ, Schölmerich J, Straub RH. An opposing time-dependent immune-modulating effect of the sympathetic nervous system conferred by altering the cytokine profile in the local lymph nodes and spleen of mice with type II collagen-induced arthritis. Arthritis Rheum. (2005) 52:1305–13. 10.1002/art.20987
    1. Stangenberg L, Burzyn D, Binstadt BA, Weissleder R, Mahmood U, Benoist C, et al. . Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature. Proc Natl Acad Sci USA. (2014) 111:11419–24. 10.1073/pnas.1410854111
    1. del Rey A, Besedovsky HO. Immune-neuro-endocrine reflexes, circuits, and networks: physiologic and evolutionary implications. Front Horm Res. (2017) 48:1–18. 10.1159/000452902
    1. MacNeil BJ, Jansen AH, Greenberg AH, Nance DM. Activation and selectivity of splenic sympathetic nerve electrical activity response to bacterial endotoxin. Am J Physiol. (1996) 270:R264–70. 10.1152/ajpregu.1996.270.1.R264
    1. Pardini BJ, Jones SB, Filkins JP. Cardiac and splenic norepinephrine turnovers in endotoxic rats. Am J Physiol. (1983) 245:H276–83. 10.1152/ajpheart.1983.245.2.H276
    1. Fuchs BA, Campbell KS, Munson AE. Norepinephrine and serotonin content of the murine spleen: its relationship to lymphocyte beta-adrenergic receptor density and the humoral immune response in vivo and in vitro. Cell Immunol. (1988) 117:339–51. 10.1016/0008-8749(88)90123-2
    1. Kohm AP, Tang Y, Sanders VM, Jones SB. Activation of antigen-specific CD4+ Th2 cells and B cells in vivo increases norepinephrine release in the spleen and bone marrow. J Immunol. (2000) 165:725–33. 10.4049/jimmunol.165.2.725
    1. Kin NW, Sanders VM. It takes nerve to tell T and B cells what to do. J Leukoc Biol. (2006) 79:1093–104. 10.1189/jlb.1105625
    1. Thellin O, Heinen E. Pregnancy and the immune system: between tolerance and rejection. Toxicology. (2003) 185:179–84. 10.1016/S0300-483X(02)00607-8
    1. Koch CA, Platt JL. Natural mechanisms for evading graft rejection: the fetus as an allograft. Springer Semin Immunopathol. (2003) 25:95–117. 10.1007/s00281-003-0136-0
    1. Guleria I, Sayegh MH. Maternal acceptance of the fetus: true human tolerance. J Immunol. (2007) 178:3345–51. 10.4049/jimmunol.178.6.3345
    1. Samstein RM, Josefowicz SZ, Arvey A, Treuting PM, Rudensky AY. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell. (2012) 150:29–38. 10.1016/j.cell.2012.05.031
    1. Owman C. Pregnancy induces degenerative and regenerative changes in the autonomic innervation of the female reproductive tract. Ciba Found Symp. (1981) 83:252–79. 10.1002/9780470720653.ch13
    1. Varol FG, Duchemin AM, Neff NH, Hadjiconstantinou M. Nerve growth factor (NGF) and NGF mRNA change in rat uterus during pregnancy. Neurosci Lett. (2000) 294:58–62. 10.1016/S0304-3940(00)01533-0
    1. Zoubina EV, Smith PG. Sympathetic hyperinnervation of the uterus in the estrogen receptor alpha knock-out mouse. Neuroscience. (2001) 103:237–44. 10.1016/S0306-4522(00)00549-2
    1. Krizsan-Agbas D, Pedchenko T, Hasan W, Smith PG. Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus. Eur J Neurosci. (2003) 18:2760–8. 10.1111/j.1460-9568.2003.03029.x
    1. Richeri A, Bianchimano P, Mármol NM, Viettro L, Cowen T, Brauer MM. Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors. J Anat. (2005) 207:125–34. 10.1111/j.1469-7580.2005.00435.x
    1. Brauer MM. Cellular and molecular mechanisms underlying plasticity in uterine sympathetic nerves. Auton Neurosci. (2008) 140:1–16. 10.1016/j.autneu.2008.02.002
    1. Latini C, Frontini A, Morroni M, Marzioni D, Castellucci M, Smith PG. Remodeling of uterine innervation. Cell Tissue Res. (2008) 334:1–6. 10.1007/s00441-008-0657-x
    1. Brauer MM, Smith PG. Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity. Auton Neurosci. (2015) 187:1–17. 10.1016/j.autneu.2014.11.009
    1. Brauer MM. Plasticity in uterine innervation: state of the art. Curr Protein Pept Sci. (2017) 18:108–19. 10.2174/1389203717666160322145411
    1. Maestroni GJ. Dendritic cell migration controlled by alpha 1b-adrenergic receptors. J Immunol. (2000) 165:6743–7. 10.4049/jimmunol.165.12.6743
    1. Maestroni GJ, Mazzola P. Langerhans cells beta 2-adrenoceptors: role in migration, cytokine production, Th priming and contact hypersensitivity. J Neuroimmunol. (2003) 144:91–9. 10.1016/j.jneuroim.2003.08.039
    1. Maestroni GJ. Sympathetic nervous system influence on the innate immune response. Ann N Y Acad Sci. (2006) 1069:195–207. 10.1196/annals.1351.017
    1. Maestroni GJ. Short exposure of maturing, bone marrow-derived dendritic cells to norepinephrine: impact on kinetics of cytokine production and Th development. J Neuroimmunol. (2002) 129:106–14. 10.1016/S0165-5728(02)00188-1
    1. Maestroni GJ. Adrenergic modulation of dendritic cells function: relevance for the immune homeostasis. Curr Neurovasc Res. (2005) 2:169–73. 10.2174/1567202053586776
    1. Manni M, Granstein RD, Maestroni G. β2-Adrenergic agonists bias TLR-2 and NOD2 activated dendritic cells towards inducing an IL-17 immune response. Cytokine. (2011) 55:380–6. 10.1016/j.cyto.2011.05.013
    1. Yanagawa Y, Matsumoto M, Togashi H. Enhanced dendritic cell antigen uptake via α2 adrenoceptor-mediated PI3K activation following brief exposure to noradrenaline. J Immunol. (2010) 185:5762–8. 10.4049/jimmunol.1001899
    1. Nakano K, Higashi T, Takagi R, Hashimoto K, Tanaka Y, Matsushita S. Dopamine released by dendritic cells polarizes Th2 differentiation. Int Immunol. (2009) 21:645–54. 10.1093/intimm/dxp033
    1. Prado C, Contreras F, González H, Díaz P, Elgueta D, Barrientos M, et al. . Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity. J Immunol. (2012) 188:3062–70. 10.4049/jimmunol.1103096
    1. Takenaka MC, Guereschi MG, Basso AS. Neuroimmune interactions: dendritic cell modulation by the sympathetic nervous system. Semin Immunopathol. (2017) 39:165–176. 10.1007/s00281-016-0590-0
    1. Burnstock G. Cotransmission in the autonomic nervous system. Handb Clin Neurol. (2013) 117:23–35. 10.1016/B978-0-444-53491-0.00003-1
    1. Beresford L, Orange O, Bell EB, Miyan JA. Nerve fibres are required to evoke a contact sensitivity response in mice. Immunology. (2004) 111:118–25. 10.1111/j.1365-2567.2004.01786.x
    1. Alonso R, Flament H, Lemoine S, Sedlik C, Bottasso E, Péguillet I, et al. . Induction of anergic or regulatory tumor-specific CD4+ T cells in the tumor-draining lymph node. Nat Commun. (2018) 9:2113. 10.1038/s41467-018-04524-x
    1. Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol. (2003) 3:331–41. 10.1038/nri1057
    1. Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat Med. (2005) 11:S45–53. 10.1038/nm1213

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren