免疫系统有助于子宫内膜异位症的病理生理学。产生粒细胞巨噬细胞集落刺激因子 (GM-CSF) 的 ThGM 细胞在子宫内膜异位症发病机制中的作用仍不清楚。为了分析ThGM细胞在子宫内膜异位症中的特征，建立了小鼠子宫内膜异位症模型。根据表面标志物和细胞内蛋白的表达，通过流式细胞术测量脾脏、腹膜液 (PF) 和子宫内膜异位病变 (EL) 中的 ThGM 细胞。根据趋化因子受体表达谱对活 ThGM 细胞进行分类，并通过共培养测定确定它们对其他 CD4 T 细胞亚群的影响。进行过继转移测定来表征 ThGM 细胞对子宫内膜异位症的作用。我们发现 ThGM 细胞存在于子宫内膜异位 PF 和 EL 中。活 EL ThGM 细胞富含 CD4 CXCR3-CCR8-CCR4 CCR10 T 细胞。 EL ThGM 细胞差异表达白细胞介素 35 受体 (IL-35R)，由 IL-35R 子集和 IL-35R- 子集组成。 IL-35R 亚群比 IL-35R 亚群表达较少的 GM-CSF、白细胞介素 2 (IL-2) 和肿瘤坏死因子 α (TNF-α)，并且增殖较慢。同时，IL-35R亚群对Th1和Th17细胞功能的促进作用弱于IL-35R-亚群。 ThGM 细胞转移不影响 EL 发育，但显着减轻 PF 和 EL 中的促炎细胞因子。白介素 35 (IL-35) 是 IL-35R 的配体，以 IL-35R 依赖性方式抑制 ThGM 细胞功能和增殖。总之，PF 和 EL 中的 ThGM 细胞可能会加剧子宫内膜异位炎症。 IL-35 可能通过 IL-35R 抑制 ThGM 细胞的功能。版权所有 © 2023。由 Elsevier Ltd 出版。

The immune system contributes to the pathophysiology of endometriosis. The role of ThGM cells, which produce granulocyte macrophage-colony-stimulating factor (GM-CSF), in the pathogenesis of endometriosis remains unknown. To analyze the features of ThGM cells in endometriosis, a mouse endometriosis model was established. ThGM cells in the spleen, peritoneal fluid (PF), and endometriotic lesions (EL) were measured by flow cytometry, based on the expression of surface markers and intracellular proteins. Live ThGM cells were sorted according to chemokine receptor expression profiles and their effects on other CD4+ T cell subsets were determined by co-culture assays. An adoptive transfer assay was performed to characterize the effect of ThGM cells on endometriosis. We found that ThGM cells were present in endometriotic PF and EL. Live EL ThGM cells were enriched in CD4+CXCR3-CCR8-CCR4+CCR10+ T cells. EL ThGM cells differentially express interleukin-35 receptor (IL-35R), consisting of an IL-35R+ subset and an IL-35R- subset. The IL-35R+ subset expressed less GM-CSF, interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α) and proliferated slower than the IL-35R- subset. Meanwhile, the IL-35R+ subset was weaker than the IL-35R- subset in promoting the functions of Th1 and Th17 cells. ThGM cell transfer did not influence EL development but significantly alleviated pro-inflammatory cytokines in PF and ELs. Interleukin-35 (IL-35), the ligand of IL-35R, suppressed ThGM cell function and proliferation in an IL-35R-dependent manner. In summary, ThGM cells in the PF and ELs might exacerbate endometriotic inflammation. IL-35 might suppress the function of ThGM cells via IL-35R.Copyright © 2023. Published by Elsevier Ltd.