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T Cell-Related Endometrial Gene Expression in Normal and Complicated Pregnancies

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Abstract

T cell immunity is critical for implantation and maintenance of pregnancy. The balance between T helper (Th)1/Th2 and Th17/T regulatory cell (Treg) immunities determines the pregnancy outcome. The predominant expression of Th2 and Treg immunities at the maternal-fetal interface was related to normal pregnancy, while the balance biased to Th1 and Th17 immunities is associated with reproductive disorders, such as recurrent implantation failures, recurrent pregnancy losses, preeclampsia, and preterm labor. T cell immunity can be evaluated by investigating lymphocyte subsets, cytokines, transcription factors, and gene expressions in the tissue (endometrium/decidua) and peripheral blood. Interestingly, various endometrial gene expression patterns have been reported to be associated with specific gynecological and obstetrical disorders. Therefore, analysis of endometrial genes responsible for the T cell subsets and related cytokines and factors will help us to understand the underlying immunopathology of reproductive failures and obstetrical complications and develop an efficient therapeutic strategy. In this review, we aim to deliberate the role of T cell immunity, which is vital to sustaining an adequate maternal-fetal response, immune homeostasis, and maintenance of pregnancy by assessing changes in T cell subsets and endometrial/decidual gene expression patterns in normal and complicated pregnancies.

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References

  1. Mosmann TR, Li L, Hengartner H, Kagi D, Fu W, Sad S. Differentiation and functions of T cell subsets. Ciba Found Symp. 1997;204:148–54; discussion 54–8.

    CAS  PubMed  Google Scholar 

  2. Chatterjee P, Chiasson VL, Bounds KR, Mitchell BM. Regulation of the anti-inflammatory cytokines interleukin-4 and interleukin-10 during pregnancy. Front Immunol. 2014;5:253.

    PubMed  PubMed Central  Google Scholar 

  3. 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):601–10.

    Article  CAS  PubMed  Google Scholar 

  4. Berger A. Th1 and Th2 responses: what are they? BMJ. 2000;321(7258):424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aluvihare VR, Betz AG. The role of regulatory T cells in alloantigen tolerance. Immunol Rev. 2006;212:330–43.

    Article  CAS  PubMed  Google Scholar 

  6. Li X, Wang B, Li Y, Wang L, Zhao X, Zhou X, et al. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice. J Ethnopharmacol. 2013;145(1):241–53.

    Article  CAS  PubMed  Google Scholar 

  7. Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology. 2016;148(1):13–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Martinez GJ, Nurieva RI, Yang XO, Dong C. Regulation and function of proinflammatory TH17 cells. Ann N Y Acad Sci. 2008;1143:188–211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu ZZ, Sun GQ, Hu XH, Kwak-Kim J, Liao AH. The transdifferentiation of regulatory T and Th17 cells in autoimmune/inflammatory diseases and its potential implications in pregnancy complications. Am J Reprod Immunol. 2017;78:e12657.

    Article  CAS  Google Scholar 

  10. Powell RM, Lissauer D, Tamblyn J, Beggs A, Cox P, Moss P, et al. Decidual T cells exhibit a highly differentiated phenotype and demonstrate potential fetal specificity and a strong transcriptional response to IFN. J Immunol. 2017;199(10):3406–17.

    Article  CAS  PubMed  Google Scholar 

  11. 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):353–6.

    Article  CAS  PubMed  Google Scholar 

  12. Clark DA, Chaouat G. Regulatory T cells and reproduction: how do they do it? J Reprod Immunol. 2012;96(1–2):1–7.

    Article  CAS  PubMed  Google Scholar 

  13. Kwak-Kim JY, Chung-Bang HS, Ng SC, Ntrivalas EI, Mangubat CP, Beaman KD, 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):767–73.

    Article  CAS  PubMed  Google Scholar 

  14. Lee SK, Kim JY, Hur SE, Kim CJ, Na BJ, Lee M, et al. An imbalance in interleukin-17-producing T and Foxp3(+) regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod. 2011;26(11):2964–71.

    Article  CAS  PubMed  Google Scholar 

  15. Santner-Nanan B, Peek MJ, Khanam R, Richarts L, Zhu E, Fazekas de St Groth B, et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009;183(11):7023–30.

    Article  CAS  PubMed  Google Scholar 

  16. Zahran AM, Zharan KM, Hetta HF. Significant correlation between regulatory T cells and vitamin D status in term and preterm labor. J Reprod Immunol. 2018;129:15–22.

    Article  CAS  PubMed  Google Scholar 

  17. Wang WJ, Hao CF, Yi L, Yin GJ, Bao SH, Qiu LH, et al. 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):164–70.

    Article  CAS  PubMed  Google Scholar 

  18. Koucky M, Malickova K, Cindrova-Davies T, Germanova A, Parizek A, Kalousova M, et al. Low levels of circulating T-regulatory lymphocytes and short cervical length are associated with preterm labor. J Reprod Immunol. 2014;106:110–7.

    Article  PubMed  Google Scholar 

  19. Kwak-Kim J, Bao S, Lee SK, Kim JW, Gilman-Sachs A. Immunological modes of pregnancy loss: inflammation, immune effectors, and stress. Am J Reprod Immunol. 2014;72(2):129–40.

    Article  CAS  PubMed  Google Scholar 

  20. Gleicher N, Kushnir VA, Barad DH. Redirecting reproductive immunology research toward pregnancy as a period of temporary immune tolerance. J Assist Reprod Genet. 2017;34(4):425–30.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Erlebacher A. Why isn’t the fetus rejected? Curr Opin Immunol. 2001;13(5):590–3.

    Article  CAS  PubMed  Google Scholar 

  22. 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. Curr Opin Immunol. 2000;12(6):731–7.

    Article  CAS  PubMed  Google Scholar 

  23. Gaunt G, Ramin K. Immunological tolerance of the human fetus. Am J Perinatol. 2001;18(6):299–312.

    Article  CAS  PubMed  Google Scholar 

  24. Bonney EA. Alternative theories: pregnancy and immune tolerance. J Reprod Immunol. 2017;123:65–71.

    Article  PubMed  Google Scholar 

  25. Collins MK, Tay CS, Erlebacher A. Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice. J Clin Invest. 2009;119(7):2062–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007;117(5):1175–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Vacca P, Cantoni C, Vitale M, Prato C, Canegallo F, Fenoglio D, et al. Crosstalk between decidual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression. Proc Natl Acad Sci. 2010;107(26):11918–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Torry DS, Hinrichs M, Torry RJ. Determinants of placental vascularity. Am J Reprod Immunol. 2004;51(4):257–68.

    Article  PubMed  Google Scholar 

  29. Vacca P, Montaldo E, Croxatto D, Loiacono F, Canegallo F, Venturini PL, et al. Identification of diverse innate lymphoid cells in human decidua. Mucosal Immunol. 2015;8(2):254–64.

    Article  CAS  PubMed  Google Scholar 

  30. Lima PD, Zhang J, Dunk C, Lye SJ, Croy BA. Leukocyte driven-decidual angiogenesis in early pregnancy. Cell Mol Immunol. 2014;11(6):522–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bulmer JN, Williams PJ, Lash GE. Immune cells in the placental bed. Int J Dev Biol. 2010;54(2–3):281–94.

    Article  PubMed  Google Scholar 

  32. Lissauer D, Kilby MD, Moss P. Maternal effector T cells within decidua: the adaptive immune response to pregnancy? Placenta. 2017;60:140–4.

    Article  CAS  PubMed  Google Scholar 

  33. Nancy P, Tagliani E, Tay CS, Asp P, Levy DE, Erlebacher A. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface. Science. 2012;336(6086):1317–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rosenblum MD, Way SS, Abbas AK. Regulatory T cell memory. Nat Rev Immunol. 2016;16(2):90–101.

    Article  CAS  PubMed  Google Scholar 

  35. Kieffer TE, Faas MM, Scherjon SA, Prins JR. Pregnancy persistently affects memory T cell populations. J Reprod Immunol. 2017;119:1–8.

    Article  CAS  PubMed  Google Scholar 

  36. Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 2012;490(7418):102–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bonney EA. Maternal tolerance is not critically dependent on interleukin-4. Immunology. 2001;103(3):382–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Clark DA, Chaouat G, Arck PC, Mittruecker HW, Levy GA. Cutting edge: cytokine-dependent abortion in CBA × DBA/2 mice is mediated by the procoagulant fgl2 prothombinase. J Immunol. 1998;160(2):545–9.

    CAS  PubMed  Google Scholar 

  39. Murphy SP, Tayade C, Ashkar AA, Hatta K, Zhang J, Croy BA. Interferon gamma in successful pregnancies. Biol Reprod. 2009;80(5):848–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Miyazaki S, Tsuda H, Sakai M, Hori S, Sasaki Y, Futatani T, et al. Predominance of Th2-promoting dendritic cells in early human pregnancy decidua. J Leukoc Biol. 2003;74(4):514–22.

    Article  CAS  PubMed  Google Scholar 

  41. Ramhorst R, Fraccaroli L, Aldo P, Alvero AB, Cardenas I, Leirós CP, et al. Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells. Am J Reprod Immunol. 2012;67(1):17–27.

    Article  CAS  PubMed  Google Scholar 

  42. Zenclussen AC, Gerlof K, Zenclussen ML, Sollwedel A, Bertoja AZ, Ritter T, et al. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am J Pathol. 2005;166(3):811–22.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Robertson SA, Care AS, Moldenhauer LM. Regulatory T cells in embryo implantation and the immune response to pregnancy. J Clin Invest. 2018;128(10):4224–35.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Agbayani G, Wachholz K, Chattopadhyay A, Gurnani K, Murphy SP, Krishnan L. Modulation of Th17 and regulatory T-cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection. Am J Reprod Immunol. 2017;78:e12742.

    Article  CAS  Google Scholar 

  45. Logiodice F, Lombardelli L, Kullolli O, Haller H, Maggi E, Rukavina D, et al. Decidual interleukin-22-producing CD4+ T cells (Th17/Th0/IL-22+ and Th17/Th2/IL-22+, Th2/IL-22+, Th0/IL-22+), which also produce IL-4, are involved in the success of pregnancy. Int J Mol Sci. 2019;20(2):E428.

    Article  PubMed  CAS  Google Scholar 

  46. Lissauer D, Piper K, Goodyear O, Kilby MD, Moss PA. Fetal-specific CD8+ cytotoxic T cell responses develop during normal human pregnancy and exhibit broad functional capacity. J Immunol. 2012;189(2):1072–80.

    Article  CAS  PubMed  Google Scholar 

  47. Piper KP, McLarnon A, Arrazi J, Horlock C, Ainsworth J, Kilby MD, et al. Functional HY-specific CD8+ T cells are found in a high proportion of women following pregnancy with a male fetus. Biol Reprod. 2007;76(1):96–101.

    Article  CAS  PubMed  Google Scholar 

  48. Tilburgs T, Strominger JL. CD8+ effector T cells at the fetal-maternal interface, balancing fetal tolerance and antiviral immunity. Am J Reprod Immunol. 2013;69(4):395–407.

    Article  CAS  PubMed  Google Scholar 

  49. Zeng W, Liu X, Liu Z, Zheng Y, Yu T, Fu S, et al. Deep surveying of the transcriptional and alternative splicing signatures for decidual CD8+ T cells at the first trimester of human healthy pregnancy. Front Immunol. 2018;9:937.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Tilburgs T, Schonkeren D, Eikmans M, Nagtzaam NM, Datema G, Swings GM, et al. Human decidual tissue contains differentiated CD8+ effector-memory T cells with unique properties. J Immunol. 2010;185(7):4470–7.

    Article  CAS  PubMed  Google Scholar 

  51. Sheridan BS, Lefrançois L. Regional and mucosal memory T cells. Nat Immunol. 2011;12(6):485–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tanikawa N, Ohtsu A, Kawahara-Miki R, Kimura K, Matsuyama S, Iwata H, et al. Age-associated mRNA expression changes in bovine endometrial cells in vitro. Reprod Biol Endocrinol. 2017;15(1):63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Forde N, Duffy GB, McGettigan PA, Browne JA, Mehta JP, Kelly AK, et al. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiol Genomics. 2012;44(16):799–810.

    Article  CAS  PubMed  Google Scholar 

  54. Averaimo S, Milton RH, Duchen MR, Mazzanti M. Chloride intracellular channel 1 (CLIC1): sensor and effector during oxidative stress. FEBS Lett. 2010;584(10):2076–84.

    Article  CAS  PubMed  Google Scholar 

  55. Fuertes MB, Molinero LL, Toscano MA, Ilarregui JM, Rubinstein N, Fainboim L, et al. Regulated expression of galectin-1 during T-cell activation involves Lck and Fyn kinases and signaling through MEK1/ERK, p38 MAP kinase and p70S6 kinase. Mol Cell Biochem. 2004;267(1–2):177–85.

    Article  CAS  PubMed  Google Scholar 

  56. Deak M, Hornung A, Novak J, Demydenko D, Szabo E, Czibula A, et al. Novel role for galectin-1 in T-cells under physiological and pathological conditions. Immunobiology. 2015;220(4):483–9.

    Article  CAS  PubMed  Google Scholar 

  57. Rabinovich GA, Toscano MA. Turning ‘sweet’ on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nat Rev Immunol. 2009;9(5):338–52.

    Article  CAS  PubMed  Google Scholar 

  58. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005;6(12):1245–52.

    Article  CAS  PubMed  Google Scholar 

  59. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011;1221(1):80–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gnainsky Y, Granot I, Aldo P, Barash A, Or Y, Mor G, et al. Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action. Reproduction. 2015;149(1):75–85.

    Article  CAS  PubMed  Google Scholar 

  61. Ledee N, Munaut C, Aubert J, Serazin V, Rahmati M, Chaouat G, et al. Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages. J Pathol. 2011;225(4):554–64.

    Article  PubMed  Google Scholar 

  62. Ledee-Bataille N, Bonnet-Chea K, Hosny G, Dubanchet S, Frydman R, Chaouat G. Role of the endometrial tripod interleukin-18, -15, and -12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure. Fertil Steril. 2005;83(3):598–605.

    Article  CAS  PubMed  Google Scholar 

  63. Petitbarat M, Rahmati M, Serazin V, Dubanchet S, Morvan C, Wainer R, et al. TWEAK appears as a modulator of endometrial IL-18 related cytotoxic activity of uterine natural killers. PLoS One. 2011;6(1):e14497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lei MZ, Qin LJ, Zhao DD, Wang AH, Zhao XJ, Jin YP, et al. Tumor necrosis factor-like weak inducer of apoptosis regulates the phenotype and cytotoxic activity of goat uterine natural killer cells. J Anim Sci. 2015;93(2):589–97.

    Article  CAS  PubMed  Google Scholar 

  65. Ledee N, Petitbarat M, Chevrier L, Vitoux D, Vezmar K, Rahmati M, et al. The uterine immune profile may help women with repeated unexplained embryo implantation failure after in vitro fertilization. Am J Reprod Immunol. 2016;75(3):388–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jasper MJ, Tremellen KP, Robertson SA. Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod. 2006;12(5):301–8.

    Article  CAS  PubMed  Google Scholar 

  67. Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013;99(1):63.

    Article  Google Scholar 

  68. Kwak-Kim J, Skariah A, Wu L, Salazar D, Sung N, Ota K. Humoral and cellular autoimmunity in women with recurrent pregnancy losses and repeated implantation failures: a possible role of vitamin D. Autoimmun Rev. 2016;15(10):943–7.

    Article  CAS  PubMed  Google Scholar 

  69. Liu Y-S, Wu L, Tong X-H, Wu L-M, He G-P, Zhou G-X, et al. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2011;65(5):503–11.

    Article  CAS  PubMed  Google Scholar 

  70. Wu L, Luo LH, Zhang YX, Li Q, Xu B, Zhou GX, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Lee SK, Kim JY, Han AR, Hur SE, Kim CJ, Kim TH, et al. Intravenous immunoglobulin G improves pregnancy outcome in women with recurrent pregnancy losses with cellular immune abnormalities. Am J Reprod Immunol. 2016;75(1):59–68.

    Article  CAS  PubMed  Google Scholar 

  72. Muyayalo KP, Li ZH, Mor G, Liao AH. Modulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2018;80(4):e13018.

    Article  PubMed  Google Scholar 

  73. Haas J, Korporal M, Schwarz A, Balint B, Wildemann B. The interleukin-7 receptor alpha chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis. Eur J Immunol. 2011;41(3):845–53.

    Article  CAS  PubMed  Google Scholar 

  74. Wu L, Li J, Xu HL, Xu B, Tong XH, Kwak-Kim J, 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):454–64.

    Article  CAS  PubMed  Google Scholar 

  75. von Wolff M, Thaler CJ, Strowitzki T, Broome J, Stolz W, Tabibzadeh S. Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion. Mol Hum Reprod. 2000;6(7):627–34.

    Article  Google Scholar 

  76. Banerjee P, Ghosh S, Dutta M, Subramani E, Khalpada J, Roychoudhury S, et al. Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage. PLoS One. 2013;8(11):e80940.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Tersigni C, D’Ippolito S, Di Nicuolo F, Marana R, Valenza V, Masciullo V, et al. Recurrent pregnancy loss is associated to leaky gut: a novel pathogenic model of endometrium inflammation. J Transl Med. 2018;16(1):102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol. 2012;188(1):21–8.

    Article  CAS  PubMed  Google Scholar 

  79. Lala PK, Kennedy TG, Parhar RS. Suppression of lymphocyte alloreactivity by early gestational human decidua. II. Characterization of the suppressor mechanisms. Cell Immunol. 1988;116(2):411–22.

    Article  CAS  PubMed  Google Scholar 

  80. Ye Y, Vattai A, Ditsch N, Kuhn C, Rahmeh M, Mahner S, et al. Prostaglandin E2 receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses. Endocr Connect. 2018;7(5):749–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cornelius DC, Cottrell J, Amaral LM, LaMarca B. Inflammatory mediators: a causal link to hypertension during preeclampsia. Br J Pharmacol. 2019;176(12):1914–21.

    Article  CAS  PubMed  Google Scholar 

  82. Amaral LM, Kiprono L, Cornelius DC, Shoemaker C, Wallace K, Moseley J, et al. Progesterone supplementation attenuates hypertension and the autoantibody to the angiotensin II type I receptor in response to elevated interleukin-6 during pregnancy. Am J Obstet Gynecol. 2014;211(2):158 e1–6.

    Article  CAS  Google Scholar 

  83. Darmochwal-Kolarz D, Saito S, Tabarkiewicz J, Kolarz B, Rolinski J, Leszczynska-Gorzelak B, et al. Apoptosis signaling is altered in CD4+CD25+FoxP3+ T regulatory lymphocytes in pre-eclampsia. Int J Mol Sci. 2012;13(6):6548–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Salazar Garcia MD, Mobley Y, Henson J, Davies M, Skariah A, Dambaeva S, et al. Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia. J Reprod Immunol. 2018;125:25–31.

    Article  CAS  PubMed  Google Scholar 

  85. Wallukat G, Homuth V, Fischer T, Lindschau C, Horstkamp B, Jupner A, et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest. 1999;103(7):945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, et al. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci U S A. 2009;106(35):14948–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Tian M, Zhang Y, Liu Z, Sun G, Mor G, Liao A. The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats. Sci Rep. 2016;6:27683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang Z, Liu H, Shi Y, Xu N, Wang Y, Li A, et al. Increased circulating Th22 cells correlated with Th17 cells in patients with severe preeclampsia. Hypertens Pregnancy. 2017;36(1):100–7.

    Article  CAS  PubMed  Google Scholar 

  89. Vianna P, Mondadori AG, Bauer ME, Dornfeld D, Chies JA. HLA-G and CD8+ regulatory T cells in the inflammatory environment of pre-eclampsia. Reproduction. 2016;152(6):741–51.

    Article  CAS  PubMed  Google Scholar 

  90. Vrachnis N, Vitoratos N, Iliodromiti Z, Sifakis S, Deligeoroglou E, Creatsas G. Intrauterine inflammation and preterm delivery. Ann N Y Acad Sci. 2010;1205:118–22.

    Article  CAS  PubMed  Google Scholar 

  91. Park JC, Kim DJ, Kwak-Kim J. Upregulated amniotic fluid cytokines and chemokines in emergency cerclage with protruding membranes. Am J Reprod Immunol. 2011;66(4):310–9.

    Article  CAS  PubMed  Google Scholar 

  92. Gomez-Lopez N, Olson DM, Robertson SA. Interleukin-6 controls uterine Th9 cells and CD8(+) T regulatory cells to accelerate parturition in mice. Immunol Cell Biol. 2016;94(1):79–89.

    Article  CAS  PubMed  Google Scholar 

  93. Makhseed M, Raghupathy R, El-Shazly S, Azizieh F, Al-Harmi JA, Al-Azemi MM. Pro-inflammatory maternal cytokine profile in preterm delivery. Am J Reprod Immunol. 2003;49(5):308–18.

    Article  CAS  PubMed  Google Scholar 

  94. Gargano JW, Holzman C, Senagore P, Thorsen P, Skogstrand K, Hougaard DM, et al. Mid-pregnancy circulating cytokine levels, histologic chorioamnionitis and spontaneous preterm birth. J Reprod Immunol. 2008;79(1):100–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Gomez-Lopez N, Laresgoiti-Servitje E. T regulatory cells: regulating both term and preterm labor? Immunol Cell Biol. 2012;90(10):919–20.

    Article  CAS  PubMed  Google Scholar 

  96. Ito M, Nakashima A, Hidaka T, Okabe M, Bac ND, Ina S, et al. A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour. J Reprod Immunol. 2010;84(1):75–85.

    Article  CAS  PubMed  Google Scholar 

  97. Elovitz MA, Baron J, Phillippe M. The role of thrombin in preterm parturition. Am J Obstet Gynecol. 2001;185(5):1059–63.

    Article  CAS  PubMed  Google Scholar 

  98. Shankar R, Johnson MP, Williamson NA, Cullinane F, Purcell AW, Moses EK, et al. Molecular markers of preterm labor in the choriodecidua. Reprod Sci. 2010;17(3):297–310.

    Article  CAS  PubMed  Google Scholar 

  99. Rinaldi SF, Makieva S, Saunders PT, Rossi AG, Norman JE. Immune cell and transcriptomic analysis of the human decidua in term and preterm parturition. Mol Hum Reprod. 2017;23(10):708–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Wu, L., Liao, A., Gilman-Sachs, A., Kwak-Kim, J. (2020). T Cell-Related Endometrial Gene Expression in Normal and Complicated Pregnancies. In: Kwak-Kim, J. (eds) Endometrial Gene Expression. Springer, Cham. https://doi.org/10.1007/978-3-030-28584-5_3

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-28583-8

  • Online ISBN: 978-3-030-28584-5

  • eBook Packages: MedicineMedicine (R0)

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