Activated CD8(+) tissue-resident memory T cells impact the endometrial receptivity in minimal/mild endometriosis.

Endometrial immune disorders create an inhospitable endometrial environment for embryonic nidation in endometriosis. CD8 + tissue resident memory T cells (CD8 +TRM) are abundant tissue resident immune cells in endometrium, but the effect of CD8 +TRM on endometrial receptivity of endometriosis remains unexplored. We collected endometrium tissue to explore the number and function of CD8 +TRM in eutopic endometrium of endometriosis and controls through flow cytometry. Then we co-cultured CD8 +TRM with endometrial stromal cells (ESCs) to explore the influence of CD8 +TRM on the expression of endometrial receptivity markers in ESCs. Next, we established mice models to find the number and function of CD8 +TRM and find immune intervention target of it in vivo. We found that the cytotoxicity, degranulation, and inflammatory cytokine expressed by CD8 +TRM were higher in endometriosis patients than in controls during secretory phase. CD8 +TRM inhibited the expression of HOXA10, FOXO1, IGFBP-1 and PRL of ESCs in a co-culture system. The expression of HOXA10, FOXO1, IGFBP-1 and PRL of ESCs were improved when blocking IFN-γ. And the number of CD8 +TRM and its cytotoxicity and expression of inflammatory cytokine were higher in endometriosis mice models than sham operation controls. After intraperitoneal injected anti-IFN-γ or anti-CD8α, the expression of endometrial receptivity makers was increased. These findings demonstrated that CD8 +TRM participate in the pro-inflammatory endometrial immune microenvironment and affect the expression of endometrial receptivity and decidualization markers in the eutopic endometrium of endometriosis patients and endometriosis mice models. CD8 +TRM and its IFN-γ secretion could be probably immunotherapeutic target for defective endometrial receptivity of endometriosis.