Li Chaoquan, Liu Wanting, Fu Aoni, Yang Haotian, Yi Guanghui
Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Institute of Pharmacy and Pharmacology, Hunan province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China.
Cell Immunol. 2025 May-Jun;411-412:104957. doi: 10.1016/j.cellimm.2025.104957. Epub 2025 Apr 28.
Efferocytosis, the process by which apoptotic cells (ACs) are recognized and cleared by phagocytes, is a critical mechanism in maintaining intestinal immune homeostasis and promoting the resolution of inflammation. Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation, wherein defective efferocytosis contributes to the accumulation of ACs, secondary necrosis, and sustained mucosal damage. This review delineates the molecular mechanisms underlying efferocytosis and systematically examines its functional roles across five key intestinal phagocytic cell types: macrophages, dendritic cells (DCs), neutrophils, intestinal epithelial cells (IECs), and Paneth cells (PCs). Particular emphasis is placed on the dysregulation of efferocytosis capacity in IBD pathogenesis and the consequences of impaired apoptotic cell clearance in both professional and non-professional phagocytes. Furthermore, we evaluate emerging therapeutic strategies designed to restore or enhance efferocytosis, including modulation of macrophage polarization, LC3-associated phagocytosis pathways, nanotechnology-enabled delivery systems, and stem cell-based interventions. A comprehensive understanding of cell-type-specific efferocytosis in the intestinal microenvironment offers promising directions for the development of targeted, inflammation-resolving therapies for IBD.
胞葬作用是指凋亡细胞被吞噬细胞识别并清除的过程，是维持肠道免疫稳态和促进炎症消退的关键机制。炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC），其特征为慢性肠道炎症，其中胞葬作用缺陷会导致凋亡细胞积累、继发性坏死和持续性黏膜损伤。本综述阐述了胞葬作用的分子机制，并系统研究了其在五种关键肠道吞噬细胞类型中的功能作用，这五种细胞类型分别为巨噬细胞、树突状细胞（DC）、中性粒细胞、肠上皮细胞（IEC）和潘氏细胞（PC）。特别强调了胞葬作用能力失调在IBD发病机制中的作用，以及专业和非专业吞噬细胞中凋亡细胞清除受损的后果。此外，我们评估了旨在恢复或增强胞葬作用的新兴治疗策略，包括调节巨噬细胞极化、LC3相关吞噬途径、纳米技术递送系统和基于干细胞的干预措施。全面了解肠道微环境中细胞类型特异性胞葬作用为开发针对IBD的靶向性、炎症消退疗法提供了有前景的方向。
