Decreased CCL5 expression in endometrial stromal cells induces deficient CCR5<sup>+</sup>CD4<sup>+</sup> 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<sup>+</sup> T...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
China Science Publishing & Media Ltd.
2025-01-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024178 |
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| Summary: | 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<sup>+</sup> T cells can regulate EMS through diverse cytokines, the inflammatory response, and angiogenesis. CCR5<sup>+</sup>CD4<sup>+</sup> T cells exhibit increased cellular immunogenicity and play a role in infectious diseases, host defense, and cancer progression. However, the specific mechanisms of CCR5<sup>+</sup>CD4<sup>+</sup> 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<sup>+</sup>CD4<sup>+</sup> 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<sup>‒/‒</sup> mice and utilized to explore the in vivo effects of CCR5<sup>+</sup>CD4<sup>+</sup> T cells on ectopic lesions. Compared with CCR5<sup>‒</sup>CD4<sup>+</sup> T cells, CCR5<sup>+</sup>CD4<sup>+</sup> T cells display a more activated and cytotoxic phenotype. Diminished CCR5<sup>+</sup>CD4<sup>+</sup> 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<sup>‒/‒</sup> mice are more likely to generate ectopic lesions in the peritoneum of recipient mice. These findings demonstrate that the attenuated recruitment of CCR5<sup>+</sup>CD4<sup>+</sup> T cells in ectopic lesions caused by decreased production of CCL5 in ecESCs may facilitate the progression of EMS. |
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| ISSN: | 1672-9145 |