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作者

Shuang Wang, Le Xu, Xue Jiao, Xiaoyu Dong, Zhaoyang Zhong, Qianhui Ren, Xiaoxuan Liu, Ming Yuan, Guoyun Wang

作者单位

Affiliations ¹ Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province, 250000, China. ² Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, 250000, China. ³ JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China. ⁴ Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China. ⁵ Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China. ⁶ Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong Province, 250000, China. wangguoy@sdu.edu.cn. ⁷ JiNan Key Laboratory of Diagnosis and Treatment of Major Gynaecological Disease, Jinan, Shandong Province, 250000, China. wangguoy@sdu.edu.cn. ⁸ Gynecology Laboratory, Shandong Provincial Hospital, Jinan, Shandong Province, 250000, China. wangguoy@sdu.edu.cn. ⁹ Gynecology Laboratory, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, 250000, China. wangguoy@sdu.edu.cn.

刊名

BMC medicine

年份

2025

卷号

Vol.23 No.1

页码

588

ISSN

1741-7015

关键词

CD8+ T cells Endometriosis Ferroptosis GPX4 Iron overload p53.

摘要

Background: Endometriosis exhibits localised iron overload. However, the contribution of ferroptosis to EM pathogenesis remains unclear. We investigated how iron overload affects CD8⁺ T cell immune function and the underlying ferroptotic mechanisms. Methods: We collected eutopic and ectopic endometrial tissues from 57 patients with stage III-IV EM and eutopic tissues from 31 controls. Iron deposition was assessed by Prussian blue staining; CD8⁺ T cell infiltration by immunohistochemistry; and f...更多

Background: Endometriosis exhibits localised iron overload. However, the contribution of ferroptosis to EM pathogenesis remains unclear. We investigated how iron overload affects CD8⁺ T cell immune function and the underlying ferroptotic mechanisms. Methods: We collected eutopic and ectopic endometrial tissues from 57 patients with stage III-IV EM and eutopic tissues from 31 controls. Iron deposition was assessed by Prussian blue staining; CD8⁺ T cell infiltration by immunohistochemistry; and ferroptosis in CD8⁺ T cells by immunofluorescence and flow cytometry. In vitro and in vivo assays measured CD8⁺ T cell ferroptosis and endometrial stromal cell apoptosis via flow cytometry. Transwell assays evaluated cell migration. Gene and protein expression were analysed via RT-qPCR and Western Blot. We verified the effect of iron overload on the growth of lesions in vivo by constructing a mouse EM model. The role of CD8⁺ T cells in EM progression was tested using a reinfusion model. Results: In ectopic EM lesions, CD8⁺ T cells were enriched yet functionally impaired, showing increased ferrous iron accumulation and lipid peroxidation alongside decreased GPX4 expression. In vitro, iron overload reduced CD8⁺ T cell viability, elevated lipid peroxidation, and induced mitochondrial damage-effects reversed by ferroptosis inhibitors. Iron overload upregulated p53 and downregulated xCT and GPX4; p53 inhibition blocked ferroptosis, indicating a p53-dependent pathway. In vivo EM models confirmed that excess iron compromises CD8⁺ T cell function and impairs their recruitment to lesion sites. Conclusions: Iron overload induces p53-mediated inhibition of xCT/GPX4, triggering ferroptosis in CD8⁺ T cells and leading to their dysfunction. These insights into ferroptosis-CD8⁺ T cell interactions in EM may guide the development of novel immunotherapeutic strategies.收起

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