Roles of pro- and anti-inflammatory cytokines in the pathogenesis of SLE

Ding-Lei Su, Zhi-Min Lu, Min-Ning Shen, Xia Li, Ling-Yun Sun, Ding-Lei Su, Zhi-Min Lu, Min-Ning Shen, Xia Li, Ling-Yun Sun

Abstract

SLE is an autoimmune inflammatory disease in which various pro- and anti-inflammatory cytokines, including TGF-β, IL-10, BAFF, IL-6, IFN-α, IFN-γ, IL-17, and IL-23, play crucial pathogenic roles. Virtually, all these cytokines can be generated by both innate and adaptive immune cells and exert different effects depending on specific local microenvironment. They can also interact with each other, forming a complex network to maintain delicate immune homeostasis. In this paper, we elaborate on the abnormal secretion and functions of these cytokines in SLE, analyze their potential pathogenic roles, and probe into the possibility of them being utilized as targets for therapy.

Figures

Figure 1
Figure 1
Cytokine network that links innate and adaptive immunity. This figure illustrates the functions of some key cytokines secreted by several most important types of immune cells. APC refers primarily to monocytes, macrophages, and dendritic cells. In SLE, TGF-β and IL-10 mainly exhibit anti-inflammatory effects, while IL-6, BAFF, IFN-α, IFN-γ, IL-17, and IL-23 function as proinflammatory cytokines. These cytokines have cross-talks by affecting one another, thereafter constituting a complex network.

References

    1. Govinden R, Bhoola KD. Genealogy, expression, and cellular function of transforming growth factor-β. Pharmacology & Therapeutics. 2003;98(2):257–265.
    1. Yoshimura A, Wakabayashi Y, Mori T. Cellular and molecular basis for the regulation of inflammation by TGF-β. The Journal of Biochemistry. 2010;147(6):781–792.
    1. Li M, Wan YY, Sanjabi S, Robertson AKL, Flavell RA. Transforming growth factor-β regulation of immune responses. Annual Review of Immunology. 2006;24:99–146.
    1. Li MO, Flavell RA. Contextual regulation of inflammation: a duet by transforming growth factor-β and interleukin-10. Immunity. 2008;28(4):468–476.
    1. Fadok VA, Bratton DL, Konowal A, Freed PW, Westcott JY, Henson PM. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-β, PGE2, and PAF. The Journal of Clinical Investigation. 1998;101(4):890–898.
    1. Strobl H, Knapp W. TGF-β1 regulation of dendritic cells. Microbes and Infection. 1999;1(15):1283–1290.
    1. Laouar Y, Sutterwala FS, Gorelik L, Flavell RA. Transforming growth factor-β controls T helper type 1 cell development through regulation of natural killer cell interferon-γ. Nature Immunology. 2005;6(6):600–607.
    1. Wolfraim LA, Walz TM, James Z, Fernandez T, Letterio JJ. p21Cip1 and p27Kip1 act in synergy to alter the sensitivity of naive T cells to TGF-β-mediated G1 arrest through modulation of IL-2 responsiveness. The Journal of Immunology. 2004;173(5):3093–3102.
    1. Gorelik L, Constant S, Flavell RA. Mechanism of transforming growth factor β-induced inhibition of T helper type 1 differentiation. The Journal of Experimental Medicine. 2002;195(11):1499–1505.
    1. Heath VL, Murphy EE, Crain C, Tomlinson MG, O’Garra A. TGF-β1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. European Journal of Immunology. 2000;30(9):2639–2649.
    1. Ichiyama K, Yoshida H, Wakabayashi Y, et al. Foxp3 inhibits RORγt-mediated IL-17A mRNA transcription through direct interaction with RORγt. The Journal of Biological Chemistry. 2008;283(25):17003–17008.
    1. Chen W-J, Jin W-W, Hardegen N, et al. Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3. The Journal of Experimental Medicine. 2003;198(12):1875–1886.
    1. Xing Q, Su H, Cui J, Wang B. Role of Treg cells and TGF-β1 in patients with systemic lupus erythematosus: a possible relation with lupus nephritis. Immunological investigations. 2012;41(1):15–27.
    1. Antiga E, Bianco ED, Difonzo EM, Fabbri P, Caproni M. Serum levels of the regulatory cytokines transforming growth factor-β and interleukin-10 are reduced in patients with discoid lupus erythematosus. Lupus. 2011;20(6):556–560.
    1. Elbeldi-Ferchiou A, Ahmed MB, Smiti-Khanfir M, et al. Resistance to exogenous TGF-ß effects in patients with systemic lupus erythematosus. Journal of Clinical Immunology. 2011;31(4):574–583.
    1. Becker-Merok A, Eilertsen G, Nossent JC. Levels of transforming growth factor-β are low in systemic lupus erythematosus patients with active disease. The Journal of Rheumatology. 2010;37(10):2039–2045.
    1. Hammad AM, Youssef HM, El-Arman MM. Transforming growth factor beta 1 in children with systemic lupus erythematosus: a possible relation with clinical presentation of lupus nephritis. Lupus. 2006;15(9):608–612.
    1. Guo H, Leung J-C, Chan L-Y, Lui S-L, Tsang A-W, Lai K-N. Modulation of intra-pulmonary TGF-β expression by mycophenolate mofetil in lupus prone MRL/lpr mice. Lupus. 2005;14(8):583–592.
    1. Saxena V, Lienesch DW, Zhou M, et al. Dual roles of immunoregulatory cytokine TGF-β in the pathogenesis of autoimmunity-mediated organ damage. The Journal of Immunology. 2008;180(3):1903–1912.
    1. Kaplan JM, Woodworth L, Smith K, Coco J, Vitsky A, McPherson JM. Therapeutic benefit of treatment with anti-thymocyte globulin and latent TGF-β1 in the MRL/lpr lupus mouse model. Lupus. 2008;17(9):822–831.
    1. Rhodes KA, Andrew EM, Newton DJ, Tramonti D, Carding SR. A subset of IL-10-producing γδ T cells protect the liver from Listeria-elicited, CD8+ T cell-mediated injury. European Journal of Immunology. 2008;38(8):2274–2283.
    1. Yanaba K, Bouaziz JD, Matsushita T, Tsubata T, Tedder TF. The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. The Journal of Immunology. 2009;182(12):7459–7472.
    1. Vanden Eijnden S, Goriely S, De Wit D, Willems F, Goldman M. IL-23 up-regulates IL-10 and induces IL-17 synthesis by polyclonally activated naive T cells in human. European Journal of Immunology. 2005;35(2):469–475.
    1. McGeachy MJ, Bak-Jensen KS, Chen Y, et al. TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nature Immunology. 2007;8(12):1390–1397.
    1. Boonstra A, Rajsbaum R, Holman M, et al. Macrophages and myeloid dendritic cells, but not plasmacytoid dendritic cells, produce IL-10 in response to MyD88- and TRIF-dependent TLR signals, and TLR-independent signals. The Journal of Immunology. 2006;177(11):7551–7558.
    1. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology. 2001;19:683–765.
    1. Ding L, Linsley PS, Huang L-Y, Germain RN, Shevach EM. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. The Journal of Immunology. 1993;151(3):1224–1234.
    1. McBride JM, Jung T, de Vries JE, Aversa G. IL-10 alters DC function via modulation of cell surface molecules resulting in impaired T-cell responses. Cellular Immunology. 2002;215(2):162–172.
    1. Romagnani S. Biology of human TH1 and TH2 cells. Journal of Clinical Immunology. 1995;15(3):121–129.
    1. Joss A, Akdis M, Faith A, Blaser K, Akdis CA. IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. European Journal of Immunology. 2000;30(6):1683–1690.
    1. Schuetze N, Schoeneberger S, Mueller U, Freudenberg MA, Alber G, Straubinger RK. IL-12 family members: differential kinetics of their TLR4-mediated induction by Salmonella Enteritidis and the impact of IL-10 in bone marrow-derived macrophages. International Immunology. 2005;17(5):649–659.
    1. Llorente L, Zou W, Levy Y, et al. Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. The Journal of Experimental Medicine. 1995;181(3):839–844.
    1. Levy Y, Brouet JC. Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. The Journal of Clinical Investigation. 1994;93(1):424–428.
    1. Park YB, Lee SK, Kim D-S, Lee J, Lee CH, Song CH. Elevated interleukin-10 levels correlated with disease activity in systemic lupus erythematosus. Clinical and Experimental Rheumatology. 1998;16(3):283–288.
    1. Lauwerys BR, Garot N, Renauld JC, Houssiau FA. Interleukin-10 blockade corrects impaired in vitro cellular immune responses of systemic lupus erythematosus patients. Arthritis & Rheumatism. 2000;43(9):1976–1981.
    1. Llorente L, Richaud-Patin Y, Garcia-Padilla C, et al. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic Lupus erythematosus. Arthritis & Rheumatism. 2000;43(8):1790–1800.
    1. Wang H-J, Xu J, Ji X, et al. The abnormal apoptosis of T cell subsets and possible involvement of IL-10 in systemic lupus erythematosus. Cellular Immunology. 2005;235(2):117–121.
    1. Nakano S, Morimoto S, Suzuki J, et al. Role of pathogenic auto-antibody production by Toll-like receptor 9 of B cells in active systemic lupus erythematosus. Rheumatology. 2008;47(2):145–149.
    1. Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M. Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. The Journal of Experimental Medicine. 1994;179(1):305–310.
    1. Yin Z-N, Bahtiyar G, Zhang N-Z, et al. IL-10 regulates murine lupus. The Journal of Immunology. 2002;169(4):2148–2155.
    1. Undeutsch R, Humrich JY, Papendieck A, Riemekasten G. CD4 T cells producing IL-10 have a beneficial effect in murine lupus. Annals of the Rheumatic Diseases. 2011;70(supplement 2):A70–A73.
    1. Blenman KRM, Duan B, Xu Z, et al. IL-10 regulation of lupus in the NZM2410 murine model. Laboratory Investigation. 2006;86(11):1136–1148.
    1. Hiran T. IL-6 and its receptor. International Reviews of Immunology. 1998;16:249–284.
    1. Naka T, Nishimoto N, Kishimoto T. The paradigm of IL-6: from basic science to medicine. Arthritis Research. 2002;4(supplement 3):S233–S242.
    1. Dienz O, Eaton SM, Bond JP, et al. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells. The Journal of Experimental Medicine. 2009;206(1):69–78.
    1. Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F. Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nature Immunology. 2007;8(9):942–949.
    1. Suzuki H, Yasukawa K, Saito T, et al. Serum soluble interleukin-6 receptor in MRL/lpr mice is elevated with age and mediates the interleukin-6 signal. European Journal of Immunology. 1993;23(5):1078–1082.
    1. Cash H, Relle M, Menke J, et al. Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Fas lpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus. The Journal of Rheumatology. 2010;37(1):60–70.
    1. Finck BK, Chan B, Wofsy D. Interleukin 6 promotes murine lupus in NZB/NZW F1 mice. The Journal of Clinical Investigation. 1994;94(2):585–591.
    1. Mihara M, Takagi N, Takeda Y, Ohsugi Y. IL-6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/WF1 mice. Clinical & Experimental Immunology. 1998;112(3):397–402.
    1. Ryffel B, Car BD, Gunn H, Roman D, Hiestand P, Mihatsch MJ. Interleukin-6 exacerbates glomerulonephritis in (NZBxNZW)F1 mice. The American Journal of Pathology. 1994;144(5):927–937.
    1. Grondal G, Gunnarsson I, Ronnelid J, Rogberg S, Klareskog L, Lundberg I. Cytokine production, serum levels and disease activity in systemic lupus erythematosus. Clinical and Experimental Rheumatology. 2000;18(5):565–570.
    1. Tsai C-Y, Wu T-H, Yu C-L, Lu J-Y, Tsai Y-Y. Increased excretions of β2-microglobulin, IL-6, and IL-8 and decreased excretion of Tamm-Horsfall glycoprotein in urine of patients with active lupus nephritis. Nephron. 2000;85(3):207–214.
    1. Herrera-Esparza R, Barbosa-Cisneros O, Villalobos-Hurtado R, Avalos-Díaz E. Renal expression of IL-6 and TNFα genes in lupus nephritis. Lupus. 1998;7(3):154–158.
    1. Hirohata S, Kanai Y, Mitsuo A, Tokano Y, Hashimoto H. Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicenter retrospective study. Clinical Rheumatology. 2009;28(11):1319–1323.
    1. Ripley BJM, Goncalves B, Isenberg DA, Latchman DS, Rahman A. Raised levels of interleukin 6 in systemic lupus erythematosus correlate with anaemia. Annals of the Rheumatic Diseases. 2005;64(6):849–853.
    1. Al-Mutairi S, Al-Awadhi A, Raghupathy R, et al. Lupus patients with pulmonary involvement have a pro-inflammatory cytokines profile. Rheumatology International. 2007;27(7):621–630.
    1. Eilertsen G, Nikolaisen C, Merok AB, Nossent JC. Interleukin-6 promotes arthritis and joint deformation in patients with systemic lupus erythematosus. Lupus. 2011;20(6):607–613.
    1. Linker-Israeli M, Deans RJ, Wallace DJ, Prehn J, Ozeri-Chen T, Klinenberg JR. Elevated levels of endogenous IL-6 in systemic lupus erythematosus: a putative role in pathogenesis. The Journal of Immunology. 1991;147(1):117–123.
    1. Kitani A, Hara M, Hirose T, et al. Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression. Clinical & Experimental Immunology. 1992;88(1):75–83.
    1. Hillion S, Garaud S, Devauchelle V, et al. Interleukin-6 is responsible for aberrant B-cell receptor-mediated regulation of RAG expression in systemic lupus erythematosus. Immunology. 2007;122(3):371–380.
    1. Takeno M, Nagafuchi H, Kaneko S, et al. Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production. The Journal of Immunology. 1997;158(7):3529–3538.
    1. Sun KH, Yu CL, Tang SJ, Sun GH. Monoclonal anti-double-stranded DNA autoantibody stimulates the expression and release of IL-1β, IL-6, IL-8, IL-10 and TNF-α from normal human mononuclear cells involving in the lupus pathogenesis. Immunology. 2000;99(3):352–360.
    1. Takemura T, Yoshioka K, Murakami K, et al. Cellular localization of inflammatory cytokines in human glomerulonephritis. Virchows Archiv. 1994;424(5):459–464.
    1. Malide D, Russo P, Bendayan M. Presence of tumor necrosis factor alpha and interleukin-6 in renal mesangial cells of lupus nephritis patients. Human Pathology. 1995;26(5):558–564.
    1. Pflegerl P, Vesely P, Hantusch B, et al. Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(48):20423–20428.
    1. Wan SG, Xia CQ, Morel L. IL-6 produced by dendritic cells from lupus-prone mice inhibits CD4+CD25+ T cell regulatory functions. The Journal of Immunology. 2007;178(1):271–279.
    1. Pramanik R, Jørgensen TN, Xin H, Kotzin BL, Choubey D. Interleukin-6 induces expression of Ifi202, an interferon-inducible candidate gene for lupus susceptibility. The Journal of Biological Chemistry. 2004;279(16):16121–16127.
    1. Illei GG, Shirota Y, Yarboro CH, et al. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis & Rheumatism. 2010;62(2):542–552.
    1. Khan WN. B cell receptor and BAFF receptor signaling regulation of B cell homeostasis. The Journal of Immunology. 2009;183(6):3561–3567.
    1. MacKay F, Schneider P. Cracking the BAFF code. Nature Reviews Immunology. 2009;9(7):491–502.
    1. López-Fraga M, Fernández R, Albar JP, Hahne M. Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Reports. 2001;2(10):945–951.
    1. Hsu BL, Harless SM, Lindsley RC, Hilbert DM, Cancro MP. Cutting edge: BLyS enables survival of transitional and mature B cells through distinct mediators. The Journal of Immunology. 2002;168(12):5993–5996.
    1. O’Connor BP, Raman VS, Erickson LD, et al. BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells. The Journal of Experimental Medicine. 2004;199(1):91–98.
    1. Daridon C, Youinou P, Pers JO. BAFF, APRIL, TWE-PRIL: who’s who? Autoimmunity Reviews. 2008;7(4):267–271.
    1. Benson MJ, Dillon SR, Castigli E, et al. Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. The Journal of Immunology. 2008;180(6):3655–3659.
    1. Hatzoglou A, Roussel J, Bourgeade MF, et al. TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-κB, Elk-1, c-jun N-terminal kinase, and p38 mitogen-activated protein kinase. The Journal of Immunology. 2000;165(3):1322–1330.
    1. Xu LG, Shu HB. TNFR-associated factor-3 is associated with BAFF-R and negatively regulates BAFF-R-mediated NF-κB activation and IL-10 production. The Journal of Immunology. 2002;169(12):6883–6889.
    1. Craxton A, Magaletti D, Ryan EJ, Clark EA. Macrophage- and dendritic cell-dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF. Blood. 2003;101(11):4464–4471.
    1. Mecklenbräuker I, Kalled SL, Lettges M, Mackay F, Tarakhovsky A. Regulation of B-cell survival by BAFF-dependent PKCδ-mediated nuclear signalling. Nature. 2004;431(7007):456–461.
    1. George-Chandy A, Trysberg E, Eriksson K. Raised intrathecal levels of APRIL and BAFF in patients with systemic lupus erythematosus: relationship to neuropsychiatric symptoms. Arthritis Research & Therapy. 2008;10(4) Article ID R97.
    1. Kayagaki N, Yan M, Seshasayee D, et al. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-κB2. Immunity. 2002;17(4):515–524.
    1. Petri M, Stohl W, Chatham W, et al. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis & Rheumatism. 2008;58(8):2453–2459.
    1. Kim J, Gross JA, Dillon SR, Min J-K, Elkon KB. Increased BCMA expression in lupus marks activated B cells, and BCMA receptor engagement enhances the response to TLR9 stimulation. Autoimmunity. 2011;44(2):69–81.
    1. Yoshimoto K, Takahashi Y, Ogasawara M, et al. Aberrant expression of BAFF in T cells of systemic lupus erythematosus, which is recapitulated by a human T cell line, Loucy. International Immunology. 2006;18(7):1189–1196.
    1. Morimoto S, Nakano S, Watanabe T, et al. Expression of B-cell activating factor of the tumour necrosis factor family (BAFF) in T cells in active systemic lupus erythematosus: the role of BAFF in T cell-dependent B cell pathogenic autoantibody production. Rheumatology. 2007;46(7):1083–1086.
    1. Smedby KE, Askling J, Mariette X, Baecklund E. Autoimmune and inflammatory disorders and risk of malignant lymphomas—an update. Journal of Internal Medicine. 2008;264(6):514–527.
    1. Katsenelson N, Kanswal S, Puig M, Mostowski H, Verthelyi D, Akkoyunlu M. Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated immunoglobulin secretion. European Journal of Immunology. 2007;37(7):1785–1795.
    1. Treml LS, Carlesso G, Hoek KL, et al. TLR stimulation modifies BLyS receptor expression in follicular and marginal zone B cells. The Journal of Immunology. 2007;178(12):7531–7539.
    1. Chu VT, Enghard P, Schürer S, et al. Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosus. Arthritis & Rheumatism. 2009;60(7):2083–2093.
    1. Löfström B, Backlin C, Pettersson T, Lundberg IE, Baecklund E. Expression of APRIL in diffuse large B cell lymphomas from patients with systemic lupus erythematosus and rheumatoid arthritis. The Journal of Rheumatology. 2011;38(9):1891–1897.
    1. He B, Raab-Traub N, Casali P, Cerutti A. EBV-encoded latent membrane protein 1 cooperates with BAFF/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching. The Journal of Immunology. 2003;171(10):5215–5224.
    1. He B, Chadburn A, Jou E, Schattner EJ, Knowles DM, Cerutti A. Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. The Journal of Immunology. 2004;172(5):3268–3279.
    1. Lech-Maranda E, Baseggio L, Bienvenu J, et al. Interleukin-10 gene promoter polymorphisms influence the clinical outcome of diffuse large B-cell lymphoma. Blood. 2004;103(9):3529–3534.
    1. Blay JY, Burdin N, Rousset F, et al. Serum interleukin-10 in non-Hodgkin’s lymphoma: a prognostic factor. Blood. 1993;82(7):2169–2174.
    1. Furie R, Stohl W, Ginzler EM, et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis Research & Therapy. 2008;10(5) Article ID R109.
    1. Wallace DJ, Stohl W, Furie RA, et al. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Care & Research. 2009;61(9):1168–1178.
    1. Jacobi AM, Huang W, Wang T, et al. Effect of long-term belimumab treatment on B cells in systemic lupus erythematosus: extension of a phase II, double-blind, placebo-controlled, dose-ranging study. Arthritis & Rheumatism. 2010;62(1):201–210.
    1. Navarra S, Guzman R, Gallacher A, et al. Belimumab, a BLyS-specific inhibitor, reduced disease activity, flares and prednisone use in patients with active SLE: efficacy and safety results from the phase 3 BLISS-52 study. In: Proceedings of the American College of Rheumatology Annual Scientific Meeting; 2009; Philadelphia, Pa, USA.
    1. GlaxoSmithKline. GlaxoSmithKline and Human Genome Sciences announce positive results in second of two phase 3 trials of Benlysta in systemic lupus erythematosus. 2009, .
    1. Vugmeyster Y, Seshasayee D, Chang W, et al. A soluble BAFF antagonist, BR3-Fc, decreases peripheral blood B cells and lymphoid tissue marginal zone and follicular B cells in cynomolgus monkeys. The American Journal of Pathology. 2006;168(2):476–489.
    1. Mackay F, Schneider P, Rennert P, Browning J. BAFF and APRIL: a tutorial on B cell survival. Annual Review of Immunology. 2003;21:231–264.
    1. Dall’Era M, Chakravarty E, Wallace D, et al. Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus: results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial. Arthritis & Rheumatism. 2007;56(12):4142–4150.
    1. Dall’Era M, Wofsy D. Systemic lupus erythematosus clinical trials—an interim analysis. Nature Reviews Rheumatology. 2009;5(6):348–351.
    1. Pestka S, Krause CD, Walter MR. Interferons, interferon-like cytokines, and their receptors. Immunological Reviews. 2004;202:8–32.
    1. Takeuchi O, Akira S. Innate immunity to virus infection. Immunological Reviews. 2009;227(1):75–86.
    1. Theofilopoulos AN, Baccala R, Beutler B, Kono DH. Type I interferons (α/β) in immunity and autoimmunity. Annual Review of Immunology. 2005;23:307–336.
    1. Rönnblom L, Eloranta ML, Alm GV. The type I interferon system in systemic lupus erythematosus. Arthritis & Rheumatism. 2006;54(2):408–420.
    1. Pittau E, Bogliolo A, Tinti A, et al. Development of arthritis and hypothyroidism during alpha-interferon therapy for chronic hepatitis C. Clinical and Experimental Rheumatology. 1997;15(4):415–419.
    1. Rönnblom L, Alm GV. A pivotal role for the natural interferon α-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. The Journal of Experimental Medicine. 2001;194(12):F59–F63.
    1. Banchereau J, Pascual V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity. 2006;25(3):383–392.
    1. Liu Z, Bethunaickan R, Huang W, et al. Interferon-α accelerates murine systemic lupus erythematosus in a T cell-dependent manner. Arthritis & Rheumatism. 2011;63(1):219–229.
    1. Santer DM, Yoshio T, Minota S, Möller T, Elkon KB. Potent induction of IFN-α and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. The Journal of Immunology. 2009;182(2):1192–1201.
    1. Thacker SG, Berthier CC, Mattinzoli D, Rastaldi MP, Kretzler M, Kaplan MJ. The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction. The Journal of Immunology. 2010;185(7):4457–4469.
    1. Li J, Fu Q, Cui H, et al. Interferon-α priming promotes lipid uptake and macrophage-derived foam cell formation: a novel link between interferon-α and atherosclerosis in lupus. Arthritis & Rheumatism. 2011;63(2):492–502.
    1. Santiago-Raber ML, Baccala R, Haraldsson KM, et al. Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. The Journal of Experimental Medicine. 2003;197(6):777–788.
    1. Braun D, Geraldes P, Demengeot J. Type I Interferon controls the onset and severity of autoimmune manifestations in lpr mice. Journal of Autoimmunity. 2003;20(1):15–25.
    1. Mathian A, Gallegos M, Pascual V, Banchereau J, Koutouzov S. Interferon-α induces unabated production of short-lived plasma cells in pre-autoimmune lupus-prone (NZB×NZW)F1 mice but not in BALB/c mice. European Journal of Immunology. 2011;41(3):863–872.
    1. Deng Y, Tsao B-P. Genetic susceptibility to systemic lupus erythematosus in the genomic era. Nature Reviews Rheumatology. 2010;6(12):683–692.
    1. Wenzel J, Zahn S, Bieber T, Tüting T. Type I interferon-associated cytotoxic inflammation in cutaneous lupus erythematosus. Archives of Dermatological Research. 2009;301(1):83–86.
    1. Feng X, Wu H, Grossman JM, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis & Rheumatism. 2006;54(9):2951–2962.
    1. Rozzo SJ, Allard JD, Choubey D, et al. Evidence for an interferon-inducible gene, Ifi202, in the susceptibility to systemic lupus. Immunity. 2001;15(3):435–443.
    1. Wetter DA, Davis MDP. Lupus-like syndrome attributable to anti-tumor necrosis factor α therapy in 14 patients during an 8-year period at mayo clinic. Mayo Clinic Proceedings. 2009;84(11):979–984.
    1. Palucka AK, Blanck JP, Bennett L, Pascual V, Banchereau J. Cross-regulation of TNF and IFN-α in autoimmune diseases. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(9):3372–3377.
    1. de Rycke L, Baeten D, Kruithof E, Van den Bosch F, Veys EM, De Keyser F. Infliximab, but not etanercept, induces IgM anti-double-stranded DNA autoantibodies as main antinuclear reactivity: biologic and clinical implications in autoimmune arthritis. Arthritis & Rheumatism. 2005;52(7):2192–2201.
    1. Iwamoto S, Iwai SI, Tsujiyama K, et al. TNF-α drives human CD14+ monocytes to differentiate into CD70+ dendritic cells evoking Th1 and Th17 responses. The Journal of Immunology. 2007;179(3):1449–1457.
    1. Kleindienst P, Wiethe G, Lutz MB, Brocker T. Simultaneous induction of CD4 T cell tolerance and CD8 T cell immunity by semimature dendritic cells. The Journal of Immunology. 2005;174(7):3941–3947.
    1. Blanco P, Palucka AK, Gill M, Pascual V, Banchereau J. Induction of dendritic cell differentiation by IFN-α in systemic lupus erythematosus. Science. 2001;294(5546):1540–1543.
    1. Mohty M, Vialle-Castellano A, Nunes JA, Isnardon D, Olive D, Gaugler B. IFN-α skews monocyte differentiation into toll-like receptor 7-expressing dendritic cells with potent functional activities. The Journal of Immunology. 2003;171(7):3385–3393.
    1. Ravelli A. Macrophage activation syndrome. Current Opinion in Rheumatology. 2002;14(5):548–552.
    1. Billiau AD, Roskams T, Van Damme-Lombaerts R, Matthys P, Wouters C. Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-γ-producing lymphocytes and IL-6- and TNF-α-producing macrophages. Blood. 2005;105(4):1648–1651.
    1. Forastiero RR, Martinuzzo ME, de Larrañaga GF. Circulating levels of tissue factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies. Lupus. 2005;14(2):129–136.
    1. Bennett L, Palucka AK, Arce E, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. The Journal of Experimental Medicine. 2003;197(6):711–723.
    1. Yao Y, Richman L, Higgs BW, et al. Neutralization of interferon-α/β-inducible genes and downstream effect in a phase I trial of an anti-interferon-α monoclonal antibody in systemic lupus erythematosus. Arthritis & Rheumatism. 2009;60(6):1785–1796.
    1. Gottenberg JE, Chiocchia G. Dendritic cells and interferon-mediated autoimmunity. Biochimie. 2007;89(6-7):856–871.
    1. Verthelyi D, Petri M, Ylamus M, Klinman DM. Disassociation of sex hormone levels and cytokine production in SLE patients. Lupus. 2001;10(5):352–358.
    1. Harigai M, Kawamoto M, Hara M, Kubota T, Kamatani N, Miyasaka N. Excessive production of IFN-γ in patients with systemic lupus erythematosus and its contribution to induction of B lymphocyte stimulator/B cell-activating factor/TNF ligand superfamily-13B. The Journal of Immunology. 2008;181(3):2211–2219.
    1. Hayashi T. Therapeutic strategies for SLE involving cytokines: mechanism-oriented therapies especially IFN-γ targeting gene therapy. Journal of Biomedicine and Biotechnology. 2010;2010:19 pages. Article ID 461641.
    1. Viallard JF, Pellegrin JL, Ranchin V, et al. Th1 (IL-2, interferon-gamma (IFN-γ)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) Clinical & Experimental Immunology. 1999;115(1):189–195.
    1. Lit LCW, Wong CK, Li EKM, Tam LS, Lam CWK, Lo YMD. Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus. The Journal of Rheumatology. 2007;34(1):89–96.
    1. Tucci M, Lombardi L, Richards HB, Dammacco F, Silvestris F. Overexpression of interleukin-12 and T helper 1 predominance in lupus nephritis. Clinical & Experimental Immunology. 2008;154(2):247–254.
    1. Chan RW, Lai FM, Li EK, et al. Intrarenal cytokine gene expression in lupus nephritis. Annals of the Rheumatic Diseases. 2007;66(7):886–892.
    1. Nicoletti F, Di Marco R, Zaccone P, et al. Dichotomic effects of IFN-γ on the development of systemic lupus erythematosus-like syndrome in MRL-lpr/lpr mice. European Journal of Immunology. 2000;30(2):438–447.
    1. Mohan C, Datta SK. Lupus: key pathogenic mechanisms and contributing factors. Clinical Immunology and Immunopathology. 1995;77(3):209–220.
    1. Santiago-Raber ML, Baccala R, Haraldsson KM, et al. Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. The Journal of Experimental Medicine. 2003;197(6):777–788.
    1. Lawson BR, Prud’homme GJ, Chang Y, et al. Treatment of murine lupus with cDNA encoding IFN-γR/Fc. The Journal of Clinical Investigation. 2000;106(2):207–215.
    1. Steinmetz OM, Turner JE, Paust HJ, et al. CXCR3 mediates renal Th1 and Th17 immune response in murine lupus nephritis. The Journal of Immunology. 2009;183(7):4693–4704.
    1. Kim K, Cho SK, Sestak A, Namjou B, Kang C, Bae SC. Interferon-gamma gene polymorphisms associated with susceptibility to systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2010;69(6):1247–1250.
    1. Karonitsch T, Feierl E, Steiner CW, et al. Activation of the interferon-γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells. Arthritis & Rheumatism. 2009;60(5):1463–1471.
    1. Serra M, Forcales S-V, Pereira-Lopes S, Lloberas J, Celada A. Characterization of Trex1 induction by IFN-γ in murine macrophages. The Journal of Immunology. 2011;186(4):2299–2308.
    1. Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annual Review of Immunology. 2007;25:221–242.
    1. Riol-Blanco L, Lazarevic V, Awasthi A, et al. IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. The Journal of Immunology. 2010;184(4):1710–1720.
    1. Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. The Journal of Experimental Medicine. 2005;201(2):233–240.
    1. Huang X, Hua J, Shen N, Chen S. Dysregulated expression of interleukin-23 and interleukin-12 subunits in systemic lupus erythematosus patients. Modern Rheumatology. 2007;17(3):220–223.
    1. Rönnblom L, Eloranta ML, Alm GV. The type I interferon system in systemic lupus erythematosus. Arthritis & Rheumatism. 2006;54(2):408–420.
    1. Li Y, Liang WB, Li C, et al. The association between interleukin-23 receptor gene polymorphisms and systemic lupus erythematosus. DNA and Cell Biology. 2010;29(2):79–82.
    1. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annual Review of Immunology. 2007;25:821–852.
    1. Dong C. Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells. Nature Reviews Immunology. 2006;6(4):329–333.
    1. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annual Review of Immunology. 2009;27:485–517.
    1. Albanesi C, Cavani A, Girolomoni G. IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-γ and TNF-α. The Journal of Immunology. 1999;162(1):494–502.
    1. Doreau A, Belot A, Bastid J, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nature Immunology. 2009;10(7):778–785.
    1. Shah K, Lee WW, Lee SH, et al. Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus. Arthritis research & therapy. 2010;12(2) Article ID R53.
    1. Zhang Z, Kyttaris VC, Tsokos GC. The role of IL-23/IL-17 axis in lupus nephritis. The Journal of Immunology. 2009;183(5):3160–3169.
    1. Crispín JC, Oukka M, Bayliss G, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. The Journal of Immunology. 2008;181(12):8761–8766.
    1. Kwan BC, Tam LS, Lai KB, et al. The gene expression of type 17 T-helper cell-related cytokines in the urinary sediment of patients with systemic lupus erythematosus. Rheumatology. 2009;48(12):1491–1497.
    1. Crispín JC, Tsokos GC. Interleukin-17-producing T cells in lupus. Current Opinion in Rheumatology. 2010;22(5):499–503.
    1. Edgerton C, Crispín JC, Moratz CM, et al. IL-17 producing CD4+ T cells mediate accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice. Clinical Immunology. 2009;130(3):313–321.
    1. McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23-IL-17 immune pathway. Trends in Immunology. 2006;27(1):17–23.
    1. Wong CK, Lit LCW, Tam LS, Li EKM, Wong PTY, Lam CWK. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clinical Immunology. 2008;127(3):385–393.
    1. Cheng F, Guo Z, Xu H, Yan D, Li Q. Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2009;68(4):604–606.
    1. Kyttaris VC, Zhang Z, Kuchroo VK, Oukka M, Tsokos GC. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. The Journal of Immunology. 2010;184(9):4605–4609.
    1. Kikly K, Liu L, Na S, Sedgwick JD. The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation. Current Opinion in Immunology. 2006;18(6):670–675.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner