Li Yue, Li Yunyun, Lu Yewei, Lin Yikong, Wang Xiaolin, Zhu Yizhun, Zeng Qiongjing, Du Meirong
State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau SAR, China.
Department of Obstetrics and Gynecology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Acta Biochim Biophys Sin (Shanghai). 2025 Jan 7;57(5):690-700. doi: 10.3724/abbs.2024178.
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.
子宫内膜异位症（EMS）是一种良性妇科疾病，其特征是子宫内膜组织在子宫腔外生长。有证据表明，异位子宫内膜植入物患者的存活与免疫微环境失调有关。CD4⁺ T细胞可通过多种细胞因子、炎症反应和血管生成来调节EMS。CCR5⁺ CD4⁺ T细胞表现出增强的细胞免疫原性，并在传染病、宿主防御和癌症进展中发挥作用。然而，CCR5⁺ CD4⁺ T细胞在EMS中的具体机制仍不清楚。在本研究中，利用流式细胞术和RNA测序来评估EMS患者中CCR5⁺ CD4⁺ T细胞的比例和特征，采用RT-PCR和ELISA来评估异位子宫内膜基质细胞（ecESCs）产生CCL5的情况。通过C57B6野生型和CCL5⁻/⁻小鼠建立了两种EMS模型，并用于探讨CCR5⁺ CD4⁺ T细胞对异位病变的影响。与CCR5⁻ CD4⁺ T细胞相比，CCR5⁺ CD4⁺ T细胞表现出更活化和细胞毒性的表型。在EMS患者的异位病变和小鼠EMS模型中均观察到CCR5⁺ CD4⁺ T细胞减少及其产生IFN-γ的能力受损。在人ecESCs中检测到CCL5产生受损。此外，从CCL5⁻/⁻小鼠剥离的子宫内膜更有可能在受体小鼠的腹膜中产生异位病变。这些发现表明，ecESCs中CCL5产生减少导致异位病变中CCR5⁺ CD4⁺ T细胞募集减弱可能促进EMS的进展。
