Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Cells. 2023 Jul 4;12(13):1779. doi: 10.3390/cells12131779.
Crohn's disease (CD) is a chronic inflammatory bowel disease marked by relapsing, transmural intestinal inflammation driven by innate and adaptive immune responses. Autophagy is a multi-step process that plays a critical role in maintaining cellular homeostasis by degrading intracellular components, such as damaged organelles and invading bacteria. Dysregulation of autophagy in CD is revealed by the identification of several susceptibility genes, including , , , , , , and , that are involved in autophagy. In this review, the role of altered autophagy in the mucosal innate immune response in the context of CD is discussed, with a specific focus on dendritic cells, macrophages, Paneth cells, and goblet cells. Selective autophagy, such as xenophagy, ERphagy, and mitophagy, that play crucial roles in maintaining intestinal homeostasis in these innate immune cells, are discussed. As our understanding of autophagy in CD pathogenesis evolves, the development of autophagy-targeted therapeutics may benefit subsets of patients harboring impaired autophagy.
克罗恩病(CD)是一种慢性炎症性肠病,其特征是固有免疫和适应性免疫应答导致的反复发作、透壁性肠道炎症。自噬是一个多步骤的过程,通过降解细胞内成分(如受损的细胞器和入侵的细菌)在维持细胞内环境稳定方面起着关键作用。在 CD 中,自噬的失调通过鉴定几个易感性基因来揭示,这些基因包括 、 、 、 、 、 和 ,它们都参与自噬。在这篇综述中,讨论了自噬改变在 CD 背景下黏膜固有免疫反应中的作用,特别关注树突状细胞、巨噬细胞、潘氏细胞和杯状细胞。讨论了在这些固有免疫细胞中维持肠道内环境稳定中发挥关键作用的选择性自噬,如异噬、内质网自噬和线粒体自噬。随着我们对 CD 发病机制中自噬的理解的发展,针对自噬的治疗方法的发展可能会使一些自噬受损的患者受益。