Decreased CCL5 expression in endometrial stromal cells induces deficient CCR5 CD4 T cells in endometriosis.

Endometriosis (EMS) is a benign gynecological disease characterized by the growth of endometrial tissue outside the uterine cavity. Evidence shows that the survival of patients with ectopic endometrial implants is associated with a dysregulated immune microenvironment. CD4 T cells can regulate EMS through diverse cytokines, the inflammatory response, and angiogenesis. CCR5 CD4 T cells exhibit increased cellular immunogenicity and play a role in infectious diseases, host defense, and cancer progression. However, the specific mechanisms of CCR5 CD4 T cells in EMS remain unknown. In the present study, flow cytometry and RNA-seq are utilized to assess the proportions and features of CCR5 CD4 T cells in EMS patients, RT-PCR and ELISA are used to assess the production of CCL5 by ectopic endometrial stromal cells (ecESCs). Two EMS models are established through C57B6 wild-type and CCL5 mice and utilized to explore the effects of CCR5 CD4 T cells on ectopic lesions. Compared with CCR5 CD4 T cells, CCR5 CD4 T cells display a more activated and cytotoxic phenotype. Diminished CCR5 CD4 T cells and their impaired ability to produce IFN-γ are observed in the ectopic lesions of EMS patients and in murine EMS models. Impaired production of CCL5 has been detected in human ecESCs. Moreover, endometria stripped from CCL5 mice are more likely to generate ectopic lesions in the peritoneum of recipient mice. These findings demonstrate that the attenuated recruitment of CCR5 CD4 T cells in ectopic lesions caused by decreased production of CCL5 in ecESCs may facilitate the progression of EMS.