Chen Xiangqi, Wu Chuan, Tang Fei, Zhou Jingyue, Mo Li, Li Yanping, He Jinhan
Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Adv Sci (Weinh). 2025 Aug;12(30):e05067. doi: 10.1002/advs.202505067. Epub 2025 May 20.
Fibrosis, characterized by abnormal deposition of structural proteins, is a major cause of tissue dysfunction in chronic diseases. The disease burden associated with progressive fibrosis is substantial, and currently approved drugs are unable to effectively reverse it. Immune cells are increasingly recognized as crucial regulators in the pathological process of fibrosis by releasing effector molecules, such as cytokines, chemokines, extracellular vesicles, metabolites, proteases, or intercellular contact. Therefore, targeting the immune microenvironment can be a potential strategy for fibrosis reduction and reversion. This review summarizes the recent advances in the understanding of the immune microenvironment in fibrosis including phenotypic and functional transformations of immune cells and the interaction of immune cells with other cells. The novel opportunities for the discovery and development of drugs for immune microenvironment remodeling and their associated challenges are also discussed.
纤维化以结构蛋白异常沉积为特征，是慢性疾病中组织功能障碍的主要原因。与进行性纤维化相关的疾病负担巨大，目前获批的药物无法有效逆转它。免疫细胞通过释放效应分子（如细胞因子、趋化因子、细胞外囊泡、代谢产物、蛋白酶或细胞间接触），越来越被认为是纤维化病理过程中的关键调节因子。因此，靶向免疫微环境可能是减少和逆转纤维化的潜在策略。本综述总结了对纤维化免疫微环境理解的最新进展，包括免疫细胞的表型和功能转变以及免疫细胞与其他细胞的相互作用。还讨论了免疫微环境重塑药物发现和开发的新机遇及其相关挑战。
