Immunologic regulation in pregnancy: from mechanism to therapeutic strategy for immunomodulation

Shyi-Jou Chen, Yung-Liang Liu, Huey-Kang Sytwu, Shyi-Jou Chen, Yung-Liang Liu, Huey-Kang Sytwu

Abstract

The immunologic interaction between the fetus and the mother is a paradoxical communication that is regulated by fetal antigen presentation and/or by recognition of and reaction to these antigens by the maternal immune system. There have been significant advances in understanding of abnormalities in the maternal-fetal immunologic relationship in the placental bed that can lead to pregnancy disorders. Moreover, immunologic recognition of pregnancy is vital for the maintenance of gestation, and inadequate recognition of fetal antigens may cause abortion. In this paper, we illustrate the complex immunologic aspects of human reproduction in terms of the role of human leukocyte antigen (HLA), immune cells, cytokines and chemokines, and the balance of immunity in pregnancy. In addition, we review the immunologic processes of human reproduction and the current immunologic therapeutic strategies for pathological disorders of pregnancy.

References

    1. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature. 1953;172(4379):603–606.
    1. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance’ of foreign cells. 1953. Journal of Immunology. 2010;184(1):5–8.
    1. Zinkernagel RM, Hengartner H. Protective ‘immunity’ by pre-existent neutralizing antibody titers and preactivated T cells but not by so-called ‘immunological memory’. Immunological Reviews. 2006;211:310–319.
    1. Bissenden G, Ling NR, Mackintosh P. Suppression of mixed lymphocyte reactions by pregnancy serum. Clinical and Experimental Immunology. 1980;39(1):195–202.
    1. Finn R, Hill StCA, Davis JC. Feto-maternal bidirectional mixed lymphocyte reaction and survival of fetal allograft. Lancet. 1977;2(8050):1200–1202.
    1. Harris LK. Review: trophoblast-vascular cell interactions in early pregnancy: how to remodel a vessel. Placenta. 2010;31:S93–S98.
    1. Harris LK, Smith SD, Keogh RJ, et al. Trophoblast- and vascular smooth muscle cell-derived MMP-12 mediates elastolysis during uterine spiral artery remodeling. American Journal of Pathology. 2010;177(4):2103–2115.
    1. Cartwright JE, Fraser R, Leslie K, Wallace AE, James JL. Remodelling at the maternal-fetal interface: relevance to human pregnancy disorders. Reproduction. 2010;140(6):803–813.
    1. Whitley GSJ, Cartwright JE. Cellular and molecular regulation of spiral artery remodelling: lessons from the cardiovascular field. Placenta. 2010;31(6):465–474.
    1. Bulmer JN. Immune aspects of pathology of the placental bed contributing to pregnancy pathology. Bailliere’s Clinical Obstetrics and Gynaecology. 1992;6(3):461–488.
    1. von Rango U. Fetal tolerance in human pregnancy-A crucial balance between acceptance and limitation of trophoblast invasion. Immunology Letters. 2008;115(1):21–32.
    1. Kimatrai M, Oliver C, Abadía-Molina AC, García-Pacheco JM, Olivares EG. Contractile activity of human decidual stromal cells. Journal of Clinical Endocrinology and Metabolism. 2003;88(2):844–849.
    1. Kimatrai M, Blanco O, Muñoz-Fernández R, et al. Contractile activity of human decidual stromal cells. II. Effect of interleukin-10. Journal of Clinical Endocrinology and Metabolism. 2005;90(11):6126–6130.
    1. van Nieuwenhoven ALV, Heineman MJ, Faas MM. The immunology of successful pregnancy. Human Reproduction Update. 2003;9(4):347–357.
    1. Blanco O, Tirado I, Munoz-Fernandez R, et al. Human decidual stromal cells express HLA-G: effects of cytokines and decidualization. Human Reproduction. 2008;23(1):144–152.
    1. Ober C, Hyslop T, Elias S, Weitkamp LR, Hauck WW. Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study. Human Reproduction. 1998;13(1):33–38.
    1. Blaschitz A, Hutter H, Dohr G. HLA Class I protein expression in the human placenta. Early Pregnancy. 2001;5(1):67–69.
    1. Van Rood JJ, Claas F. Both self and non-inherited maternal HLA antigens influence the immune response. Immunology Today. 2000;21(6):269–273.
    1. Hunt JS, Orr HT. HLA and maternal-fetal recognition. FASEB Journal. 1992;6(6):2344–2348.
    1. Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB Journal. 2005;19(7):681–693.
    1. Lewis JE, Coulam CB, Moore SB. Immunologic mechanisms in the maternal-fetal relationship. Mayo Clinic Proceedings. 1986;61(8):655–665.
    1. Braud VM, Allan DS, McMichael AJ. Functions of nonclassical MHC and non-MHC-encoded class I molecules. Current Opinion in Immunology. 1999;11(1):100–108.
    1. Hunt JS, Andrews GK, Wood GW. Normal trophoblasts resist induction of class I HLA. Journal of Immunology. 2010;138(8):2481–2487.
    1. Gurka G, Rocklin ME. Reproductive immunology. Journal of the American Medical Association. 1987;258(20):2983–2987.
    1. Redman CWG, McMichael AJ, Stirrat GM, Sunderland CA, Ting A. Class 1 major histocompatibility complex antigens on human extra-villous trophoblast. Immunology. 1984;52(3):457–468.
    1. Ellis SA, Sargent IL, Redman CWG, McMichael AJ. Evidence for a novel HLA antigen found on human extravillous trophoblast and a choriocarcinoma cell line. Immunology. 1986;59(4):595–601.
    1. King A, Burrows TD, Hiby SE, et al. Surface expression of HLA-C antigen by human extravillous trophoblast. Placenta. 2000;21(4):376–387.
    1. Claas FHJ, Gijbels Y, Van Der Velden-De Munck J, Van Rood JJ. Induction of B cell unresponsiveness to noninherited maternal HLA antigens during fetal life. Science. 1988;241(4874):1815–1817.
    1. Tilburgs T, Scherjon SA, van der Mast BJ, et al. Fetal-maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells. Journal of Reproductive Immunology. 2009;82(2):148–157.
    1. McMaster M, Zhou Y, Shorter S, et al. HLA-G isoforms produced by placental cytotrophoblasts and found in amniotic fluid are due to unusual glycosylation. Journal of Immunology. 1998;160(12):5922–5928.
    1. Hunt JS, Langat DL. HLA-G: a human pregnancy-related immunomodulator. Current Opinion in Pharmacology. 2009;9(4):462–469.
    1. Carosella ED, Moreau P, Le Maoult J, Le Discorde M, Dausset J, Rouas-Freiss N. HLA-G molecules: from maternal-fetal tolerance to tissue acceptance. Advances in Immunology. 2003;81:199–252.
    1. Baricordi O, Stignani M, Melchiorri L, Rizzo R. HLA-G and inflammatory diseases. Inflammation and Allergy Drug Targets. 2008;7(2):67–74.
    1. Parham P. Immunology: keeping mother at bay. Current Biology. 1996;6(6):638–641.
    1. Apps R, Gardner L, Sharkey AM, Holmes N, Moffett A. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1. European Journal of Immunology. 2007;37(7):1924–1937.
    1. Ristich V, Liang S, Zhang W, Wu J, Horuzsko A. Tolerization of dendritic cells by HLA-G. European Journal of Immunology. 2005;35(4):1133–1142.
    1. Rouas-Freiss N, Naji A, Durrbach A, Carosella ED. Tolerogenic functions of human leukocyte antigen G: from pregnancy to organ and cell transplantation. Transplantation. 2007;84(supplement 1):S21–S25.
    1. Roussev RG, Coulam CB. HLA-G and its role in implantation (review) Journal of Assisted Reproduction and Genetics. 2007;24(7):288–295.
    1. Noronha LE, Antczak DF. Maternal immune responses to trophoblast: the contribution of the horse to pregnancy immunology. American Journal of Reproductive Immunology. 2010;64(4):231–244.
    1. Bacon SJ, Ellis SA, Antczak DF. Control of expression of major histocompatibility complex genes in horse trophoblast. Biology of Reproduction. 2002;66(6):1612–1620.
    1. Donaldson WL, Oriol JG, Pelkaus CL, Antczak DF. Paternal and maternal major histocompatibility complex class I antigens are expressed co-dominantly by equine trophoblast. Placenta. 1994;15(2):123–135.
    1. Rouas-Freiss N, Gonçalves RMB, Menier C, Dausset J, Carosella ED. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(21):11520–11525.
    1. Braud VM, Allan DSJ, O’Callaghan CA, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998;391(6669):795–799.
    1. Baker JM, Bamford AI, Antczak DF. Modulation of allospecific CTL responses during pregnancy in equids: an immunological barrier to interspecies matings? Journal of Immunology. 1999;162(8):4496–4501.
    1. Lea RG, Bolton AE. The effect of horse placental tissue extracts and equine chorionic gonadotrophin on the proliferation of horse lymphocytes stimulated in vitro. Journal of Reproductive Immunology. 1991;19(1):13–23.
    1. Flaminio MJBF, Antczak DF. Inhibition of lymphocyte proliferation and activation: a mechanism used by equine invasive trophoblast to escape the maternal immune response. Placenta. 2005;26(2-3):148–159.
    1. Strominger JL. Human decidual lymphocytes and the immunobiology of pregnancy. Journal of Reproductive Immunology. 2004;62(1-2):17–18.
    1. Sanguansermsri D, Pongcharoen S. Pregnancy immunology: decidual immune cells. Asian Pacific Journal of Allergy and Immunology. 2008;26(2-3):171–181.
    1. Von Rango U, Classen-Linke I, Kertschanska S, Kemp B, Beier HM. Effects of trophoblast invasion on the distribution of leukocytes in uterine and tubal implantation sites. Fertility and Sterility. 2001;76(1):116–124.
    1. Piccinni MP. T cells in normal pregnancy and recurrent pregnancy loss. Reproductive BioMedicine Online. 2006;13(6, article no. 2439):840–844.
    1. Tekelioglu Uysal M, Edwards RG, Kisnisci HA. Ultrastructural relationships between decidua, trophoblast and lymphocytes at the beginning of human pregnancy. Journal of Reproduction and Fertility. 1975;42(3):431–438.
    1. Natarajan K, Dimasi N, Wang J, Mariuzza RA, Margulies DH. Structure and function of natural killer cell receptors: multiple molecular solutions to self, nonself discrimination. Annual Review of Immunology. 2002;20:853–885.
    1. Trinchieri G. Natural killer cells wear different hats: effector cells of innate resistance and regulatory cells of adaptive immunity and of hematopoiesis. Seminars in Immunology. 1995;7(2):83–88.
    1. Croy BA, He H, Esadeg S, et al. Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling. Reproduction. 2003;126(2):149–160.
    1. Watanabe M, Iwatani Y, Kaneda T, et al. Changes in T, B, and NK lymphocyte subsets during and after normal pregnancy. American Journal of Reproductive Immunology. 1997;37(5):368–377.
    1. Kühnert M, Strohmeier R, Stegmüller M, Halberstadt E. Changes in lymphocyte subsets during normal pregnancy. European Journal of Obstetrics Gynecology and Reproductive Biology. 1998;76(2):147–151.
    1. Moffett-King A. Natural killer cells and pregnancy. Nature Reviews Immunology. 2002;2(9):656–663.
    1. Campbell JJ, Qin S, Unutmaz D, et al. Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. Journal of Immunology. 2001;166(11):6477–6482.
    1. Searle RF, Jones RK, Bulmer JN. Phenotypic analysis and proliferative responses of human endometrial granulated lymphocytes during the menstrual cycle. Biology of Reproduction. 1999;60(4):871–878.
    1. Ritson A, Bulmer JN. Endometrial granulocytes in human decidua react with a natural-killer (NK) cell marker, NKH1. Immunology. 1987;62(2):329–331.
    1. King A. Uterine leukocytes and decidualization. Human Reproduction Update. 2000;6(1):28–36.
    1. Moffett A, Loke C. Immunology of placentation in eutherian mammals. Nature Reviews Immunology. 2006;6(8):584–594.
    1. Hanna J, Mandelboim O. When killers become helpers. Trends in Immunology. 2007;28(5):201–206.
    1. Nagamatsu T, Schust DJ. The contribution of macrophages to normal and pathological pregnancies. American Journal of Reproductive Immunology. 2010;63(6):460–471.
    1. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. Journal of Immunology. 2000;164(12):6166–6173.
    1. Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity. 2005;23(4):344–346.
    1. Gordon S. Alternative activation of macrophages. Nature Reviews Immunology. 2003;3(1):23–35.
    1. Munder M, Eichmann K, Modolell M. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: competitive regulation by CD4+ T cells correlates with Th1/Th2 phenotype. Journal of Immunology. 1998;160(11):5347–5354.
    1. Fenton MJ, Buras JA, Donnelly RP. IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human monocytes. Journal of Immunology. 1992;149(4):1283–1288.
    1. Houser BL, Tilburgs T, Hill J, Nicotra ML, Strominger JL. Two unique human decidual macrophage populations. Journal of Immunology. 2011;186(4):2633–2642.
    1. Saito S. Cytokine network at the feto-maternal interface. Journal of Reproductive Immunology. 2000;47(2):87–103.
    1. Thellin O, Coumans B, Zorzi W, Igout A, Heinen E. Tolerance to the foeto-placental ‘graft’: ten ways to support a child for nine months. Current Opinion in Immunology. 2000;12(6):731–737.
    1. Saito S, Tsukaguchi N, Hasegawa T, Michimata T, Tsuda H, Narita N. Distribution of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells. American Journal of Reproductive Immunology. 1999;42(4):240–245.
    1. Fest S, Aldo PB, Abrahams VM, et al. Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy. American Journal of Reproductive Immunology. 2007;57(1):55–66.
    1. Clark DA, Chaouat G, Clark DA, Gorczynski RM. Thinking outside the box: mechanisms of environmental selective pressures on the outcome of the materno-fetal relationship. American Journal of Reproductive Immunology. 2002;47(5):275–282.
    1. Chaouat G, Ledée-Bataille N, Dubanchet S, Zourbas S, Sandra O, Martal J. Th1/Th2 paradigm in pregnancy: paradigm lost? Cytokines in pregnancy/early abortion: reexamining the Th1/Th2 paradigm. International Archives of Allergy and Immunology. 2004;134(2):93–119.
    1. Song H, Lim H. Evidence for heterodimeric association of leukemia inhibitory factor (LIF) receptor and gp130 in the mouse uterus for LIF signaling during blastocyst implantation. Reproduction. 2006;131(2):341–349.
    1. McCracken SA, Hadfield K, Rahimi Z, Gallery ED, Morris JM. NF-κB-regulated suppression of T-bet in T cells represses Th1 immune responses in pregnancy. European Journal of Immunology. 2007;37(5):1386–1396.
    1. Miyaura H, Iwata M. Direct and indirect inhibition of Th1 development by progesterone and glucocorticoids. Journal of Immunology. 2002;168(3):1087–1094.
    1. Beagley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunology and Medical Microbiology. 2003;38(1):13–22.
    1. Heikkinen J, Möttönen M, Alanen A, Lassila O. Phenotypic characterization of regulatory T cells in the human decidua. Clinical and Experimental Immunology. 2004;136(2):373–378.
    1. Miwa N, Hayakawa S, Miyazaki S, et al. IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-γ increase in normal pregnancy but decrease in spontaneous abortion. Molecular Human Reproduction. 2005;11(12):865–870.
    1. Mellor AL, Sivakumar J, Chandler P, et al. Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy. Nature Immunology. 2001;2(1):64–68.
    1. Kropf P, Baud D, Marshall SE, et al. Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy. European Journal of Immunology. 2007;37(4):935–945.
    1. Gardner L, Moffett A. Dendritic cells in the human decidua. Biology of Reproduction. 2003;69(4):1438–1446.
    1. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nature Immunology. 2004;5(3):266–271.
    1. Blois SM, Ilarregui JM, Tometten M, et al. A pivotal role for galectin-1 in fetomaternal tolerance. Nature Medicine. 2007;13(12):1450–1457.
    1. Terness P, Kallikourdis M, Betz AG, Rabinovich GA, Saito S, Clark DA. Tolerance signaling molecules and pregnancy: IDO, galectins, and the renaissance of regulatory T cells. American Journal of Reproductive Immunology. 2007;58(3):238–254.
    1. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annual Review of Immunology. 2000;18:217–243.
    1. Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nature Immunology. 2001;2(2):102–107.
    1. Faunce DE, Stein-Streilein J. NKT cell-derived RANTES recruits APCs and CD8+ T cells to the spleen during the generation of regulatory T cells in tolerance. Journal of Immunology. 2002;169(1):31–38.
    1. Hornung D, Bentzien F, Wallwiener D, Kiesel L, Taylor RN. Chemokine bioactivity of RANTES in endometriotic and normal endometrial stromal cells and peritoneal fluid. Molecular Human Reproduction. 2001;7(2):163–168.
    1. Fraccaroli L, Alfieri J, Leiros CP, Ramhorst R. Immunomodulatory effects of chemokines during the early implantation window. Frontiers in Bioscience. 2009;1:288–298.
    1. Ramhorst R, Gutiérrez G, Corigliano A, Junovich G, Fainboim L. Implication of RANTES in the modulation of alloimmune response by progesterone during pregnancy. American Journal of Reproductive Immunology. 2007;57(2):147–152.
    1. Ramhorst R, Patel R, Corigliano A, Etchepareborda JJ, Fainboim L, Schust D. Induction of maternal tolerance to fetal alloantigens by RANTES production. American Journal of Reproductive Immunology. 2006;56(5-6):302–311.
    1. Fraccaroli L, Alfieri J, Larocca L, et al. A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation. Human Reproduction. 2009;24(1):166–175.
    1. Mantovani A, Bonecchi R, Locati M. Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nature Reviews Immunology. 2006;6(12):907–918.
    1. Nibbs RJB, Wylie SM, Yang J, Landau NR, Graham GJ. Cloning and characterization of a novel promiscuous human β-chemokine receptor D6. Journal of Biological Chemistry. 1997;272(51):32078–32083.
    1. Bonecchi R, Locati M, Galliera E, et al. Differential recognition and scavenging of native and truncated macrophage-derived chemokine (Macrophage-Derived Chemokine/CC Chemokine Ligand 22) by the D6 decoy receptor. Journal of Immunology. 2004;172(8):4972–4976.
    1. De La Torre YM, Buracchi C, Borroni EM, et al. Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(7):2319–2324.
    1. Wessels JM, Linton NF, Croy AB, Tayade C. A review of molecular contrasts between arresting and viable porcine attachment sites. American Journal of Reproductive Immunology. 2007;58(6):470–480.
    1. Garlanda C, Maina V, Martinez de la Torre Y, Nebuloni M, Locati M. Inflammatory reaction and implantation: the new entries PTX3 and D6. Placenta. 2008;29(2):129–134.
    1. Genetet N, Genetet B, Amice V, Fauchet R. Allogeneic responses in vitro induced by fetomaternal alloimmunization. American Journal of Reproductive Immunology. 1982;2(2):90–96.
    1. Takeshita A, Kondo T, Okada T, Kusakabe KT. Elevation of adipsin, a complement activating factor, in the mouse placenta during spontaneous abortion. Journal of Reproduction and Development. 2010;56(5):508–514.
    1. Nakamura O. Children’s immunology, what can we learn from animal studies (1): decidual cells induce specific immune system of feto-maternal interface. The Journal of Toxicological Sciences. 2009;34(supplement 2):S331–S339.
    1. Wang WJ, Hao CF, Yi-Lin, et al. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. Journal of Reproductive Immunology. 2010;84(2):164–170.
    1. Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD. The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Human Reproduction. 1982;25(10):2591–2596.
    1. Szanto A, Nagy L. The many faces of PPARγ: anti-inflammatory by any means? Immunobiology. 2008;213(9-10):789–803.
    1. Barak Y, Nelson MC, Ong ES, et al. PPARγ is required for placental, cardiac, and adipose tissue development. Molecular Cell. 1999;4(4):585–595.
    1. Schaiff WT, Barak Y, Sadovsky Y. The pleiotropic function of PPARγ in the placenta. Molecular and Cellular Endocrinology. 2006;249(1-2):10–15.
    1. Martin H. Role of PPAR-gamma in inflammation. Prospects for therapeutic intervention by food components. Mutation Research. 2009;669(1-2):1–7.
    1. Ewaschuk JB, Walker JW, Diaz H, Madsen KL. Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice. Journal of Nutrition. 2006;136(6):1483–1487.
    1. Kuchroo VK, Meyers JH, Umetsu DT, DeKruyff RH. TIM family of genes in immunity and tolerance. Advances in Immunology. 2006;91:227–249.
    1. Monney L, Sabatos CA, Gaglia JL, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. 2002;415(6871):536–541.
    1. Anderson AC, Anderson DE, Bregoli L, et al. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science. 2007;318(5853):1141–1143.
    1. Zhao J, Lei Z, Liu Y, et al. Human pregnancy up-regulates Tim-3 in innate immune cells for systemic immunity. Journal of Immunology. 2009;182(10):6618–6624.
    1. Chou FC, Shieh SJ, Sytwu HK. Attenuation of Th1 response through galectin-9 and T-cell Ig mucin 3 interaction inhibits autoimmune diabetes in NOD mice. European Journal of Immunology. 2009;39(9):2403–2411.
    1. Pitti RM, Marsters SA, Lawrence DA, et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998;396(6712):699–703.
    1. Yu KY, Kwon B, Ni J, Zhai Y, Ebner R, Kwon BS. A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. Journal of Biological Chemistry. 1999;274(20):13733–13736.
    1. Zhang J, Salcedo TW, Wan X, et al. Modulation of T-cell responses to alloantigens by TR6/DcR3. Journal of Clinical Investigation. 2001;107(11):1459–1468.
    1. Migone TS, Zhang J, Luo X, et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 2002;16(3):479–492.
    1. Gill RM, Hunt JS. Soluble receptor (DcR3) and cellular inhibitor of apoptosis-2 (cIAP-2) protect human cytotrophoblast cells against LIGHT-mediated apoptosis. American Journal of Pathology. 2004;165(1):309–317.
    1. Yen BL, Chan JC, Liu KJ, et al. Brief report-Human embryonic stem cell-derived mesenchymal progenitors possess strong immunosuppressive effects toward natural killer cells as well as T lymphocytes. Stem Cells. 2009;27(2):451–456.
    1. Sung HH, Juang JH, Lin YC, et al. Transgenic expression of decoy receptor 3 protects islets from spontaneous and chemical-induced autoimmune destruction in nonobese diabetic mice. Journal of Experimental Medicine. 2004;199(8):1143–1151.
    1. Wu SF, Liu TM, Lin YC, et al. Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory mechanism to clinical implication. Journal of Leukocyte Biology. 2004;75(2):293–306.
    1. Chen SJ, Wang YL, Kao JH, et al. Decoy receptor 3 ameliorates experimental autoimmune encephalomyelitis by directly counteracting local inflammation and downregulating Th17 cells. Molecular Immunology. 2009;47(2-3):567–574.
    1. Ka SM, Sytwu HK, Chang DM, Hsieh SL, Tsai PY, Chen A. Decoy receptor 3 ameliorates an autoimmune crescentic glomerulonephritis model in mice. Journal of the American Society of Nephrology. 2007;18(9):2473–2485.
    1. Makrigiannakis A, Karamouti M, Drakakis P, Loutradis D, Antsaklis A. Fetomaternal immunotolerance. American Journal of Reproductive Immunology. 2008;60(6):482–496.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever