Bibliographic Details
| Title: |
Activation of Gonadotropin-releasing Hormone Receptor Impedes the Immunosuppressive Activity of Decidual Regulatory T Cells via Deactivating the Mechanistic Target of Rapamycin Signaling. |
| Authors: |
Wang, Xuejin1 (AUTHOR), Zhong, Liangying2 (AUTHOR), Liu, Qiaodan3 (AUTHOR), Cai, Peiya4 (AUTHOR), Zhang, Peiru4 (AUTHOR), Lu, Zhilan5 (AUTHOR), Li, Xiaoqin5 (AUTHOR), Liu, Jin5 (AUTHOR) liujin@fjmu.edu.cn |
| Superior Title: |
Immunological Investigations. Jul2022, Vol. 51 Issue 5, p1330-1346. 17p. |
| Subject Terms: |
*LUTEINIZING hormone releasing hormone receptors, *REGULATORY T cells, *T cells, *RAPAMYCIN, *IMMUNOLOGICAL tolerance |
| Abstract: |
Understanding maternal immune tolerance is crucial for the development of therapeutics for immunological pregnancy complications. Decidual regulatory T cells (Tregs) play a pivotal role in the maintenance of maternal immune tolerance. Using a murine allogeneic pregnancy model in the current study, we identified the up-regulation of gonadotropin-releasing hormone receptor (GnRHR) in decidual T cell subsets including CD4+ conventional T cells, CD8+ T cells, and CD4+Foxp3+ Tregs. Using a lentivirus-mediated GnRHR overexpression system and a GnRHR agonist, we found that GnRHR activation decreased the expression of Treg functional molecules such as IL10 (IL-10), IL-35 subunit EBI3 (Ebi3), IL2RA (CD25), TNFRSF18 (GITR), ICOS, and Treg master regulator FOXP3. The functional analysis indicated that GnRHR activation impairs the ability of Tregs to inhibit conventional T cell proliferation. We also revealed that GnRHR activation suppressed the mechanistic target of rapamycin (mTOR) signaling in GnRHR-overexpressing splenic Tregs (Wild type C57BL/6 J background) and decidual Tregs. MHY1485, a potent mTOR activator, effectively abolished the effect of the GnRHR agonist and promoted the immunosuppressive capability of Tregs. Furthermore, in an adoptive transfer model, Treg-specific GnRHR knockdown increased Foxp3 expression in decidual Tregs while decreasing the production of IFN-γ and IL-17 in decidual effector CD4+ T cells and reducing the production of IFN-γ in decidual effector CD8+ T cells. Taken together, the present study unveils a novel mechanism by which the immunosuppressive function of decidual Tregs is modulated, and deepens our understanding of maternal immune tolerance. [ABSTRACT FROM AUTHOR] |
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