Interleukin 17 receptor E identifies heterogeneous T helper 17 cells in peritoneal fluid of moderate and severe endometriosis patients
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Interleukin-17 receptor E and CD27 identify distinct, metabolically heterogeneous Th17 cell subsets in endometriosis peritoneal fluid with varying pro-inflammatory cytokine production.
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Abstract
Endometriosis is a chronic inflammatory disorder resulting in pelvic pain and infertility. The role of T helper 17 (Th17) cells in endometriosis remains elusive. In this study, through detecting CXCR3, CCR4, CCR10, CCR6, interleukin-17 Receptor E (IL-17RE), and CD27, RORγt-and-IL-17A-expressing Th17 cells were distinguished and sorted from peritoneal fluid (PF) of patients with stage III and IV endometriosis. Furthermore, we found that IL-17RE and CD27 were the labels of heterogeneous PF Th17 subsets, i.e. IL-17RE-CD27- subset, IL-17RE+CD27- subset, and IL-17RE+CD27+ subset. The former two subsets expressed higher IL-17A, GM-CSF, and IL-22 and were more proliferative than the latter subset. RNA-Seq analysis on IL-17RE+ Th17 subset and IL-17RE- Th17 subset revealed up-regulation of genes involved in oxidative phosphorylation and electron transport chain in IL-17RE+ Th17 subset relative to IL-17RE- Th17 subset. Consistently, the IL-17RE+ Th17 subset produced more adenosine triphosphate (ATP) and reactive oxygen species (ROS) than IL-17RE- Th17 subset. In conclusion, this study provides a novel method to detect and isolate live PF Th17 cells from endometriosis patients and unveils the functional and metabolic heterogeneity of PF Th17 subsets. Therefore, it sheds light on the elucidation of molecular mechanisms that modulate the function of pathological Th17 cells in endometriosis.
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Cited by (7)
- Dysregulated T helper cytokines in serum and peritoneal fluid of women with endometriosis-related infertility 2026
- Targeting the IL-17C-M2 macrophage axis ameliorates fibrosis in endometriosis through MAPK/ERK signaling 2026
- Aberrant mitochondria in endometriosis: From pathogenic mechanisms to therapeutic opportunities 2026
- Therapeutic targeting of interleukin-17C signaling in carcinogenesis of endometriosis 2025
- Dissecting the causal effects of interleukin receptor-related factors and the risk of developing endometriosis: a two-sample Mendelian randomization study 2025
- Immunological aspects of endometriosis: pathophysiological mechanisms, diagnosis, autoimmunity, targeted therapy and modulation 2024
- Research Progress on the Immune-Related Pathogenesis and Treatment of Endometriosis 2023
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