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. 2024 Jul;172(3):469-485.
doi: 10.1111/imm.13786. Epub 2024 Mar 27.

The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

Zhi-Xiong Huang  1   2 , Dian-Chao Lin  1 , Hua-Ying Zhang  1   2 , Meng-Jie Yang  1   2 , Jia-Hao Chen  1   2 , Xin-Yu Ding  1   2 , Song-Juan Dai  1 , Yi-Huang Hong  1 , Gui-Shuang Liang  1 , Qi-Yuan Li  2 , Qiong-Hua Chen  1   2   3
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The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis

Zhi-Xiong Huang et al. Immunology. 2024 Jul.

Abstract

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.

Keywords: CD8+ T cells; endometriosis; endometriotic stromal cells; immune survival; single‐cell sequencing.

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References

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