# Decreased CCL5 expression in endometrial stromal cells induces deficient CCR5 +CD4 + T cells in endometriosis : Deficient CCR5 +CD4 + T cells in endometriosis

## TL;DR

This study finds that reduced CCL5 in endometrial cells leads to fewer active CCR5+CD4+ T cells, contributing to endometriosis progression.

## Contribution

The study reveals a novel mechanism linking CCL5 deficiency in stromal cells to impaired CCR5+CD4+ T cell function in endometriosis.

## Key findings

- CCR5+CD4+ T cells show a more activated and cytotoxic phenotype compared to CCR5-CD4+ T cells.
- Impaired CCR5+CD4+ T cells and reduced IFN-γ production are observed in endometriosis lesions.
- CCL5 deficiency in endometrial stromal cells correlates with increased ectopic lesion formation in mice.

## Abstract

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
in vivo 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.