The interplay between M2-like macrophages and Th17.1 cells promotes the progression of early-stage sarcoidosis

作者：Yu Zhao, Xiujuan Zhang, Dong Liang, Ning Zhu, Daibing Zhou, Shuanghui Li, Junzhu Lv, Junzhu Lv, Gulinuer Wumaier, Jing Wang, Yuzhen Zeng, Weiyuan Fang, Wanfeng Xiong, Chengwei Li, Mengqi Xu, An Cui, Ruzetuoheti Yiminniyaze, Shengqing Li, Shengqing Li · 发表于：Cell Communication and Signaling · 年份：2025 · DOI：10.1186/s12964-025-02566-5 · 被引用次数：3 · 研究领域：Sarcoidosis and Beryllium Toxicity Research、Phagocytosis and Immune Regulation、Immune cells in cancer

BACKGROUND: Sarcoidosis is pathologically characterized by non-necrotizing granulomas inflammation. Despite the high spontaneous remission rate, a remarkable number of sarcoidosis patients undergo persistent progression. Glucocorticoids are currently recommended as the first-line treatment for sarcoidosis, but the therapeutic responses showed a great heterogeneity in clinical practice. We investigated the role of macrophages and Th17.1 cells in the poor response to glucocorticoid and progression in the early-stage sarcoidosis. METHODS AND MAIN RESULTS: CyTOF was performed on the mediastinal lymph nodes and peripheral blood samples to probe the alterations of immune cells in sarcoidosis. Monocytes were enriched in sarcoidosis patients but with impaired functions of antigen processing and presentation. Meanwhile, Th17.1 cells were enriched and overactivated in sarcoidosis. Both macrophages and Th17.1 cells were recruited to the granuloma lesions by CCL2 and CXCL-9/10, respectively. The granulomas of sarcoidosis in lymph nodes were classified as 3 types: M1-like macrophage-dominated type (type I), M1/2-mixed macrophage type (type II) and M2-like macrophage-dominated type (type III). Type III granuloma with elevated Th17.1 cells and M2-like macrophages predict a poor therapeutic response of sarcoidosis patients. In addition, Th17.1 cells impaired the antigen phagocytic and processing ability of macrophages through CD47/SIRPα interaction. Blockade of CD47/SIRPα interaction signifi...