Estrogen enhanced the expression of IL‐17 by tissue‐resident memory γδT cells from uterus via interferon regulatory factor 4

Abstract

Tissue-resident memory γδT 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 tissueresident memory γδT cells were enriched both in human and murine uterus and highly expressed IL-17 that promoted the invasion of trophocytes in vitro. K E Y W O R D S CXCR3-CXCL10 chemokine axis, estrogen, IL-17, IRF-4, γδT cellsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

IL17A Suppresses IGFBP1 in Human Endometrial Stromal Cells

“…IL17A, from intrauterine γδ17T cells, which is thought to play an important role in EVT invasion, is highly abundant [23]. γδ17T cells are recruited into the uterus in response to estrogen, which increases in the blood with follicle development and induces IL17A production in γδ17T cells [69]. Therefore, their involvement in uterine function from the proliferative to secretory phases is also possible.…”

Gamma delta (γδ) T cells in the female reproductive tract: active participants or indifferent bystanders in reproductive success?

“…γδ T cells in the uterus are imprinted with a tissue-specific transcriptional program including higher expression levels of estrogen and progesterone receptors (PRs) which stimulate uterine γδ T-cell proliferation [ 47 , 51 , 52 ]. Estrogen upregulates mouse uterine γδ T-cell production of IL-17A [ 51 , 53 ] and CXCR3 [ 51 ].…”

“…γδ T cells in the uterus are imprinted with a tissue-specific transcriptional program including higher expression levels of estrogen and progesterone receptors (PRs) which stimulate uterine γδ T-cell proliferation [ 47 , 51 , 52 ]. Estrogen upregulates mouse uterine γδ T-cell production of IL-17A [ 51 , 53 ] and CXCR3 [ 51 ]. PR expression by γδ T cells positively correlates with their abundance in human peripheral blood and decidua, whereas it negatively correlates with their expression of checkpoint inhibitors T-cell immunoglobulin and ITIM domain (TIGIT) and programmed cell death 1 (PD-1), implying that progesterone signaling is favorable for γδ T-cell activity [ 52 ].…”

Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias

“…The difference between the sexes manifested at puberty, which suggests an effect of estrogen in the abundance of γδ T cells ( Caccamo et al, 2006 ). In animal models, estrogen has been shown to increase γδ T cells in the uterus ( Kang et al, 2022 ) and lymph nodes, but inhibits this population in the joints ( Andersson et al, 2015 ).…”