Journal
FASEB JOURNAL
Volume 36, Issue 2, Pages -Publisher
WILEY
DOI: 10.1096/fj.202101443RR
Keywords
CXCR3-CXCL10 chemokine axis; estrogen; IL-17; IRF-4; gamma delta T cells
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Funding
- National Natural Science Foundation of China (NSFC) [81971556]
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Tissue-resident memory gamma delta T cells in the uterus play a role in promoting trophocyte invasion through the production of IL-17. Estrogen enhances the population of gamma delta T cells in the uterus and increases IL-17 production through the estrogen receptor and interferon regulatory factor 4.
Tissue-resident memory gamma delta T cells at mucosal and epithelial sites play an important role for pathogen clearance, immunosurveillance, and participating in physiological processes. Different from other barrier sites, the immune cells in uterus face the protection against infections and tolerate an allogeneic fetus during a successful pregnancy. In the previous study. we found that tissue-resident memory gamma delta T cells were enriched both in human and murine uterus and highly expressed IL-17 that promoted the invasion of trophocytes in vitro. In the current study, we found that gamma delta T cells in uterus but not in blood or spleens expressed higher levels of estrogen receptors. The injection of estrogen into mice increased the proportion of gamma delta T cells in uterus but not in spleens in vivo via CXCR3-CXCL10 chemokine axis. In addition, we found that estrogen enhanced the production of IL-17 but not IFN-gamma in vivo and in vitro via interferon regulatory factor 4 but not ROR gamma t and pSTAT3 at mRNA and protein levels. The analysis of cell transcriptome sequence further identified multiple differentially expressed genes between estrogen and control gamma delta T cells. Our study demonstrated that estrogen directly act on gamma delta T cells in uterus to enhance the production of IL-17 that might promote the invasion of trophocytes. Furthermore, our study might provide a new idea that estrogen increased the prevalence of autoimmune diseases in women by enhancing gamma delta T cell-derived IL-17 production in uterus and uncover the critical pathological roles for estrogen in the development of autoimmune diseases.
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