The decidual expression of Interleukin-7 is upregulated in early pregnancy loss.
first trimester placenta
interleukin-7
recurrent spontaneous abortion
spontaneous abortion
Journal
American journal of reproductive immunology (New York, N.Y. : 1989)
ISSN: 1600-0897
Titre abrégé: Am J Reprod Immunol
Pays: Denmark
ID NLM: 8912860
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
01
04
2021
received:
12
01
2021
accepted:
12
04
2021
pubmed:
3
5
2021
medline:
27
1
2022
entrez:
2
5
2021
Statut:
ppublish
Résumé
Maternal immunological rejection of the semi-allogenic fetus is discussed as one of the significant factors involved in early pregnancy loss. An array of cytokines secreted by both maternal and fetal cells is involved in generating a delicate maternal immune tolerance. Interleukin-7 (IL-7) is discussed to play a key role in pro-inflammatory processes, but there is still limited insight into the pathophysiological input on placentation and embryonic development in early pregnancy loss. Cytokine level differences were identified with quantitative real-time PCR in placental tissue from spontaneous abortions (SA) (n = 18), recurrent spontaneous abortions (RSA) (n = 15), and healthy pregnancies (n = 15) at gestational weeks 7 to 14. Protein expression of IL-7 in the decidua was investigated by immunohistochemistry. IL-7-expressing cells were identified with double-immunofluorescence. Decidua of women with RSA expressed almost 51-times higher values of IL-7 in gene expression analysis. Immunohistochemistry identified a significant upregulation of IL-7 in the decidua of RSA specimens (p = .013) and in the decidua of women with SA (p = .004). Double-immunofluorescence confirmed decidual stroma cells as IL-7-expressing cells. Significantly elevated IL-7 values in the decidua of spontaneous and recurrent miscarriages imply a crucial role of the cytokine in the signaling at the feto-maternal interface of the placenta. An overexpression of IL-7 could result in early pregnancy loss by inducing a pro-inflammatory environment. Proven to be valuable in other autoimmune diseases, targeting IL-7 signaling therapeutically may prove to be a very beneficial treatment option for RSA patients.
Sections du résumé
BACKGROUND
Maternal immunological rejection of the semi-allogenic fetus is discussed as one of the significant factors involved in early pregnancy loss. An array of cytokines secreted by both maternal and fetal cells is involved in generating a delicate maternal immune tolerance. Interleukin-7 (IL-7) is discussed to play a key role in pro-inflammatory processes, but there is still limited insight into the pathophysiological input on placentation and embryonic development in early pregnancy loss.
PATIENTS AND METHODS
Cytokine level differences were identified with quantitative real-time PCR in placental tissue from spontaneous abortions (SA) (n = 18), recurrent spontaneous abortions (RSA) (n = 15), and healthy pregnancies (n = 15) at gestational weeks 7 to 14. Protein expression of IL-7 in the decidua was investigated by immunohistochemistry. IL-7-expressing cells were identified with double-immunofluorescence.
RESULTS
Decidua of women with RSA expressed almost 51-times higher values of IL-7 in gene expression analysis. Immunohistochemistry identified a significant upregulation of IL-7 in the decidua of RSA specimens (p = .013) and in the decidua of women with SA (p = .004). Double-immunofluorescence confirmed decidual stroma cells as IL-7-expressing cells.
CONCLUSION
Significantly elevated IL-7 values in the decidua of spontaneous and recurrent miscarriages imply a crucial role of the cytokine in the signaling at the feto-maternal interface of the placenta. An overexpression of IL-7 could result in early pregnancy loss by inducing a pro-inflammatory environment. Proven to be valuable in other autoimmune diseases, targeting IL-7 signaling therapeutically may prove to be a very beneficial treatment option for RSA patients.
Substances chimiques
IL7 protein, human
0
Interleukin-7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13437Informations de copyright
© 2021 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.
Références
Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM. The immunology of successful pregnancy. Hum Reprod Update. 2003;9(4):347-357.
Toth B, Haufe T, Scholz C, Kuhn C, et al. Placental interleukin-15 expression in recurrent miscarriage. Am J Reprod Immunol. 2010;64(6):402-410.
Sykes L, MacIntyre DA, Yap XJ, Teoh TG, Bennett PR. The Th1:th2 dichotomy of pregnancy and preterm labour. Mediators Inflamm. 2012;2012:967629.
Negishi Y, Takahashi H, Kuwabara Y, Takeshita T. Innate immune cells in reproduction. J Obstet Gynaecol Res. 2018;44(11):2025-2036.
Wu L, Li J, Xu HL, et al. IL-7/IL-7R signaling pathway might play a role in recurrent pregnancy losses by increasing inflammatory Th17 cells and decreasing Treg cells. Am J Reprod Immunol. 2016;76(6):454-464.
Kwak-Kim JY, Chung-Bang HS, Ng SC, Ntrivalas EI, et al. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod. 2003;18(4):767-773.
Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010;63(6):601-610.
Lee SK, Kim JY, Lee M, Gilman-Sachs A, Kwak-Kim J. Th17 and regulatory T cells in women with recurrent pregnancy loss. Am J Reprod Immunol. 2012;67(4):311-318.
Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Romagnani S, Le Bouteiller P. T helper cell mediated-tolerance towards fetal allograft in successful pregnancy. Clin Mol Allergy. 2015;13(1):9.
Makrigiannakis A, Petsas G, Toth B, Relakis K, Jeschke U. Recent advances in understanding immunology of reproductive failure. J Reprod Immunol. 2011;90(1):96-104.
Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clin Chim Acta. 2011;412(9-10):702-708.
Regan L, Rai R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14(5):839-854.
Practice Committee of American Society for Reproductive, M. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril, 2013;99(1):63.
Bender Atik R, Christiansen OB, Elson J, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open. 2018;2018(2):pp. hoy004.
Toth B, Jeschke U, Rogenhofer N, et al. Recurrent miscarriage: current concepts in diagnosis and treatment. J Reprod Immunol. 2010;85(1):25-32.
Ali S, Majid S, Ali MN, Taing S. Evaluation of T cell cytokines and their role in recurrent miscarriage. Int Immunopharmacol. 2020;82:106347.
Arck PC, Rücke M, Rose M, et al. Early risk factors for miscarriage: a prospective cohort study in pregnant women. Reprod Biomed Online. 2008;17(1):101-113.
Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol. 2009;2(2):76-83.
Wang WJ, Hao CF, Lin Y, Yin GJ, Bao SH, Qiu LH, Lin QD. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol. 2010;84(2):164-170.
Haller-Kikkatalo K, Uibo R. Clinical recommendations for the use of islet cell autoantibodies to distinguish autoimmune and non-autoimmune gestational diabetes. Clin Rev Allergy Immunol. 2016;50(1):23-33.
Tagoma A, Haller-Kikkatalo K, Roos K, Oras A, Kirss A, Ilonen J, Uibo R. Interleukin-7, T helper 1, and regulatory T-cell activity-related cytokines are increased during the second trimester of healthy pregnancy compared to non-pregnant women. Am J Reprod Immunol. 2019;82(6):e13188.
Zhu LY, Chen X, Xu ZZ, Xu L, Mao T, Zhang H. Changes and clinical significance of peripheral blood helper T lymphocyte and natural killer (NK) cells in unexplained recurrent spontaneous abortion (URSA) patients after abortion and successful pregnancy. Clin Exp Obstet Gynecol. 2015;42(1):62-66.
Fu B, Li X, Sun R, et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A. 2013;110(3):E231-E240.
Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol. 1993;151(9):4562-4573.
Li W, Geng L, Liu X, Gui W, Qi H. Recombinant adiponectin alleviates abortion in mice by regulating Th17/Treg imbalance via p38MAPK-STAT5 pathway. Biol Reprod. 2019;100(4):1008-1017.
Xu WM, Xiao ZN, Wang XB, Huang Y. IL-17 Induces Fetal Loss in a CBA/JxBALB/c mouse model, and an Anti-IL-17 antibody prevents fetal loss in a CBA/JxDBA/2 mouse model. Am J Reprod Immunol. 2016;75(1):51-58.
Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S. Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol. 2010;64(1):4-11.
Saifi B, Rezaee SA, Tajik N. Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. Reprod Biomed Online. 2014;29(4):481-489.
Lee JY, Lee M, Lee SK. Role of endometrial immune cells in implantation. Clin Exp Reprod Med. 2011;38(3):119-125.
Lee SK, Kim J y, Hur S e. An imbalance in interleukin-17-producing T and Foxp3(+) regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod. 2011;26(11):2964-2971.
Bikker A, Erik Hack C, Lafeber FPJG, van Roon JAG. Interleukin-7: a key mediator in T cell-driven autoimmunity, inflammation, and tissue destruction. Curr Pharm Des. 2012;18(16):2347-2356.
Kondrack RM, Harbertson J, Tan JT, McBreen ME, Surh CD, Bradley LM. Interleukin 7 regulates the survival and generation of memory CD4 cells. J Exp Med. 2003;198(12):1797-1806.
Seddon B, Tomlinson P, Zamoyska R. Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat Immunol. 2003;4(7):680-686.
Hillen MR, Hartgring SAY, Willis CR, et al. The additive inflammatory in vivo and in vitro effects of IL-7 and TSLP in arthritis underscore the therapeutic rationale for dual blockade. PLoS One. 2015;10(6):e0130830.
van Roon JA, Glaudemans KAFM, Bijlsma JWJ, Lafeber FPJG. Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production in joints of patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62(2):113-119.
van Roon JA, Verweij MC, Wijk MWV, Jacobs KMG, Bijlsma JWJ, Lafeber FPJG. Increased intraarticular interleukin-7 in rheumatoid arthritis patients stimulates cell contact-dependent activation of CD4(+) T cells and macrophages. Arthritis Rheum. 2005;52(6):1700-1710.
Arbelaez CA, Glatigny S, Duhen R, Eberl G, Oukka M, Bettelli E. IL-7/IL-7 receptor signaling differentially affects effector CD4+ T cell subsets involved in experimental autoimmune encephalomyelitis. J Immunol. 2015;195(5):1974-1983.
Liu X, Leung S, Wang C, et al. Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease. Nat Med. 2010;16(2):191-197.
Wu L, Luo LH, Zhang YX, et al. Alteration of Th17 and treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod Biol Endocrinol. 2014;12:74.
Kim DJ, Lee SK, Kim JY, et al. Intravenous immunoglobulin G modulates peripheral blood Th17 and Foxp3(+) regulatory T cells in pregnant women with recurrent pregnancy loss. Am J Reprod Immunol. 2014;71(5):441-450.
Ziegelmuller B, Vattai A, Kost B, et al. Expression of thyroid hormone receptors in villous trophoblasts and decidual tissue at protein and mRNA levels is downregulated in spontaneous and recurrent miscarriages. J Histochem Cytochem. 2015;63(7):511-523.
Lob S, Amann N, Kuhn C, et al. Interleukin-1 beta is significantly upregulated in the decidua of spontaneous and recurrent miscarriage placentas. J Reprod Immunol. 2021;144:103283.
Fares F, Azzam N, Fares B, Larsen S, Lindkaer-Jensen S. Benzene-poly-carboxylic acid complex, a novel anti-cancer agent induces apoptosis in human breast cancer cells. PLoS One. 2014;9(2):e85156.
Wang X, Wang G, Kunte M, Shinde V, Gorbatyuk M. Modulation of angiogenesis by genetic manipulation of ATF4 in mouse model of oxygen-induced retinopathy [corrected]. Invest Ophthalmol Vis Sci. 2013;54(9):5995-6002.
Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. 1993;14(7):353-356.
Chaouat G, Lédée-Bataille N, Zourbas S, et al. Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept. Am J Reprod Immunol. 2003;50(3):177-186.
Qian J, Zhang N, Lin J, et al. Distinct pattern of Th17/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion. Biosci Trends. 2018;12(2):157-167.
Liu YS, Wu L, Tong XH, et al. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2011;65(5):503-511.
Bikker A, Kruize AA, Wenting M, et al. Increased interleukin (IL)-7Ralpha expression in salivary glands of patients with primary Sjogren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity. Ann Rheum Dis. 2012;71(6):1027-1033.
Corthay A. How do regulatory T cells work? Scand J Immunol. 2009;70(4):326-336.
Prins JR, Gomez-Lopez N, Robertson SA. Interleukin-6 in pregnancy and gestational disorders. J Reprod Immunol. 2012;95(1-2):1-14.
Bettelli E, Carrier Y, Gao Wm, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235-238.
Kasprowicz DJ, Smallwood PS, Tyznik AJ, Ziegler SF. Scurfin (FoxP3) controls T-dependent immune responses in vivo through regulation of CD4+ T cell effector function. J Immunol. 2003;171(3):1216-1223.
Saifi B, Aflatoonian R, Tajik N, et al. T regulatory markers expression in unexplained recurrent spontaneous abortion. J Matern Fetal Neonatal Med. 2016;29(7):1175-1180.
Bao SH, Wang XP, De Lin Q, Wang WJ, Yin GJ, Qiu LH. Decidual CD4+CD25+CD127dim/- regulatory T cells in patients with unexplained recurrent spontaneous miscarriage. Eur J Obstet Gynecol Reprod Biol. 2011;155(1):94-98.
Nasu K, Sugano T, Fujisawa K, Arima K, Narahara H, Miyakawa I. Effects of interleukin-4 on the in-vitro production of cytokines by human endometrial stromal cells. Mol Hum Reprod. 2001;7(3):265-270.
Sharma S, Godbole G, Modi D. Decidual Control of Trophoblast Invasion. Am J Reprod Immunol. 2016;75(3):341-350.
Takao T, Asanoma K, Kato K, et al. Isolation and characterization of human trophoblast side-population (SP) cells in primary villous cytotrophoblasts and HTR-8/SVneo cell line. PLoS One. 2011;6(7):e21990.
Evans J, Salamonsen L a, Menkhorst E, Dimitriadis E. Dynamic changes in hyperglycosylated human chorionic gonadotrophin throughout the first trimester of pregnancy and its role in early placentation. Hum Reprod. 2015;30(5):1029-1038.
Kwak JY, Beer AE, Kim SH, Mantouvalos HP. Immunopathology of the implantation site utilizing monoclonal antibodies to natural killer cells in women with recurrent pregnancy losses. Am J Reprod Immunol. 1999;41(1):91-98.
Haas J, Korporal M, Schwarz A, Balint B, Wildeman B. The interleukin-7 receptor alpha chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis. Eur J Immunol. 2011;41(3):845-853.
Hartgring SA, Bijlsma JWJ, Lafeber FPJG, van Roon JAG. Interleukin-7 induced immunopathology in arthritis. Ann Rheum Dis. 2006;65(suppl. 3):iii69-iii74
Albareda MC, Perez-Mazliah D, Natale MA, et al. Perturbed T cell IL-7 receptor signaling in chronic Chagas disease. J Immunol. 2015;194(8):3883-3889.