Activation of Gonadotropin-releasing Hormone Receptor Impedes the Immunosuppressive Activity of Decidual Regulatory T Cells via Deactivating the Mechanistic Target of Rapamycin Signaling

References

• Aluvihare VR, Kallikourdis M, Betz AG. 2004. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol. 5:266–71.
   PubMed Web of Science ®Google Scholar
• Ander SE, Diamond MS, Coyne CB. 2019. Immune responses at the maternal-fetal interface. Sci Immunol. 4(31):eaat6114.
   Web of Science ®Google Scholar
• Battaglia M, Stabilini A, Tresoldi E. 2012. Expanding human T regulatory cells with the mTOR-inhibitor rapamycin. Methods Mol Biol. 821:279–93.
   PubMedGoogle Scholar
• Batticane N, Morale MC, Gallo F, Farinella Z, Marchetti B. 1991. Luteinizing hormone-releasing hormone signaling at the lymphocyte involves stimulation of interleukin-2 receptor expression. Endocrinology. 129:277–86.
   PubMed Web of Science ®Google Scholar
• Chen HF, Jeung EB, Stephenson M, Leung PC. 1999. Human peripheral blood mononuclear cells express gonadotropin-releasing hormone (GnRH), GnRH receptor, and interleukin-2 receptor gamma-chain messenger ribonucleic acids that are regulated by GnRH in vitro. J Clin Endocrinol Metab. 84:743–50.
   PubMed Web of Science ®Google Scholar
• Desaulniers AT, Cederberg RA, Lents CA, White BR. 2017. Expression and role of gonadotropin-releasing hormone 2 and its receptor in mammals. Front Endocrinol (Lausanne). 8:269.
   PubMed Web of Science ®Google Scholar
• Deshmukh H, Way SS. 2019. Immunological basis for recurrent fetal loss and pregnancy complications. Annu Rev Pathol. 14:185–210.
   PubMed Web of Science ®Google Scholar
• Dimova T, Nagaeva O, Stenqvist AC, Hedlund M, Kjellberg L, Strand M, Dehlin E, Mincheva-Nilsson L. 2011. Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples. Am J Reprod Immunol. 66(Suppl 1):44–56.
   PubMedGoogle Scholar
• Erkers T, Nava S, Yosef J, Ringden O, Kaipe H. 2013. Decidual stromal cells promote regulatory T cells and suppress alloreactivity in a cell contact-dependent manner. Stem Cells Dev. 22:2596–605.
   PubMed Web of Science ®Google Scholar
• Flanagan CA, Manilall A. 2017. Gonadotropin-releasing hormone (GnRH) receptor structure and GnRH binding. Front Endocrinol (Lausanne). 8:274.
   PubMed Web of Science ®Google Scholar
• Habicht A, Dada S, Jurewicz M, Fife BT, Yagita H, Azuma M, et al. 2007. A link between PDL1 and T regulatory cells in fetomaternal tolerance. J Immunol. 179:5211–19.
   PubMed Web of Science ®Google Scholar
• Heikkinen J, Mottonen M, Alanen A, Lassila O. 2004. Phenotypic characterization of regulatory T cells in the human decidua. Clin Exp Immunol. 136:373–78.
   PubMed Web of Science ®Google Scholar
• Ho HN, Chen HF, Chen SU, Chao KH, Yang YS, Huang SC, Lee TY, Gill TJ. 1995. Gonadotropin releasing hormone (GnRH) agonist induces down-regulation of the CD3+CD25+ lymphocyte subpopulation in peripheral blood. Am J Reprod Immunol. 33(3):243–52.
   Web of Science ®Google Scholar
• Lee HJ, Snegovskikh VV, Park JS, Foyouzi N, Han KT, Hodgson EJ, Guller S, Norwitz ER. 2010. Role of GnRH-GnRH receptor signaling at the maternal-fetal interface. Fertil Steril. 94(7):2680–87.
   Web of Science ®Google Scholar
• Li S, Zhang X, Zhang R, Liang Z, Liao W, Du Z,  Gao C, Liu F, Fan Y, Hong H. 2017. Hippo pathway contributes to cisplatin resistant-induced EMT in nasopharyngeal carcinoma cells. Cell Cycle. 16(17):1601–1610.
   Web of Science ®Google Scholar
• Mann DR, Ansari AA, Akinbami MA, Wallen K, Gould KG, McClure HM. 1994. Neonatal treatment with luteinizing hormone-releasing hormone analogs alters peripheral lymphocyte subsets and cellular and humorally mediated immune responses in juvenile and adult male monkeys. J Clin Endocrinol Metab. 78:292–98.
   PubMed Web of Science ®Google Scholar
• Marchetti B, Guarcello V, Morale MC, Bartoloni G, Palumbo G Jr., Raiti F, Cutuli N, Farinella Z, Scapagnini U. 1990. A physiological role for the neuropeptide luteinizing hormone-releasing hormone (LHRH) during the maturation of thymus gland function. Int J Neurosci. 51(3–4):287–89.
   Web of Science ®Google Scholar
• Moldenhauer LM, Schjenken JE, Hope CM, Green ES, Zhang B, Eldi P, Hayball JD, Barry SC, Robertson SA. 2019. Thymus-derived regulatory T cells exhibit Foxp3 epigenetic modification and phenotype attenuation after mating in mice. J Immunol. 203(3):647–657.
   Web of Science ®Google Scholar
• Morale MC, Batticane N, Bartoloni G, Guarcello V, Farinella Z, Galasso MG, Marchetti B. 1991. Blockade of central and peripheral luteinizing hormone-releasing hormone (LHRH) receptors in neonatal rats with a potent LHRH-antagonist inhibits the morphofunctional development of the thymus and maturation of the cell-mediated and humoral immune responses. Endocrinology. 128(2):1073–85.
   Web of Science ®Google Scholar
• Nguyen KA, Santos SJ, Kreidel MK, Diaz AL, Rey R, Lawson MA. 2004. Acute regulation of translation initiation by gonadotropin-releasing hormone in the gonadotrope cell line LbetaT2. Mol Endocrinol. 18:1301–12.
   PubMedGoogle Scholar
• Perrett RM, McArdle CA. 2013. Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network. Front Endocrinol (Lausanne). 4:180.
   PubMedGoogle Scholar
• Petraglia F, Genazzani AD, Aguzzoli L, Gallinelli A, De Vita D, Caruso A, Genazzani AR. 1994. Pulsatile fluctuations of plasma-gonadotropin-releasing hormone and corticotropin-releasing factor levels in healthy pregnant women. Acta Obstet Gynecol Scand. 73(4):284–89.
   Web of Science ®Google Scholar
• Ramakrishnappa N, Rajamahendran R, Lin YM, Leung PC. 2005. GnRH in non-hypothalamic reproductive tissues. Anim Reprod Sci. 88:95–113.
   PubMed Web of Science ®Google Scholar
• Schumacher A, Sharkey DJ, Robertson SA, Zenclussen AC. 2018. Immune cells at the fetomaternal interface: how the microenvironment modulates immune cells to foster fetal development. J Immunol. 201:325–34.
   PubMed Web of Science ®Google Scholar
• Sosnowski R, Mellon PL, Lawson MA. 2000. Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone. Mol Endocrinol. 14:1811–19.
   PubMedGoogle Scholar
• Standaert FE, Chew BP, De Avila D, Reeves JJ. 1992. Presence of luteinizing hormone-releasing hormone binding sites in cultured porcine lymphocytes. Biol Reprod. 46:997–1000.
   PubMed Web of Science ®Google Scholar
• Sun IH, Oh MH, Zhao L, Patel CH, Arwood ML, Xu W, Tam AJ, Blosser RL, Wen J, Powell JD. 2018. mTOR complex 1 signaling regulates the generation and function of central and effector Foxp3(+) regulatory T cells. J Immunol. 201(2):481–492.
   Web of Science ®Google Scholar
• Sung N, Mdsg S, Kwak-Kim DJ. 2015. GNRH agonist induces TH1 and TH17 immunity, while GNRH antagonist suppresses TH1 immunity. Fertil Steril. 104(Supplement):E61.
   Google Scholar
• Sung N, Salazar Garcia MD, Dambaeva S, Beaman KD, Gilman-Sachs A, Kwak-Kim J. 2016. Gonadotropin-releasing hormone analogues lead to pro-inflammatory changes in T lymphocytes. Am J Reprod Immunol. 76:50–58.
   PubMed Web of Science ®Google Scholar
• Wang WJ, Liu FJ, Xin-Liu, Hao CF, Bao HC, Qu QL, Liu XM. 2014. Adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA/JxBALB/c mouse model. Hum Reprod. 29(5):946–52.
   Web of Science ®Google Scholar
• Zeng H, Yang K, Cloer C, Neale G, Vogel P, Chi H. 2013. mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature. 499:485–90.
   PubMed Web of Science ®Google Scholar