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肠道免疫的离子通道调节。

Ion channel regulation of gut immunity.

机构信息

Department of Anesthesiology, The Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO.

Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, China.

出版信息

J Gen Physiol. 2023 Feb 6;155(2). doi: 10.1085/jgp.202113042. Epub 2022 Dec 2.

Abstract

Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut's immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been detected in multiple cell types throughout the GI tract. By regulating membrane properties and intracellular biochemical signaling, ion channels play a critical role in synchronized signaling among diverse cellular components in the gut that orchestrates the GI immune response. This work focuses on the role of ion channels in immune cells, non-immune resident cells, and neuroimmune interactions in the gut at the steady state and pathological conditions. Understanding the cellular and molecular basis of ion channel signaling in these immune-related pathways and initial testing of pharmacological intervention will facilitate the development of ion channel-based therapeutic approaches for the treatment of intestinal inflammation.

摘要

越来越多的证据表明,胃肠道(GI)的稳态取决于包括肠道上皮细胞、免疫系统以及支配肠道的内在和外在神经在内的许多细胞网络之间的通讯。胃肠道,尤其是结肠,是肠道微生物组的大本营,它可以动态调节免疫功能。肠道免疫系统还提供了针对进入胃肠道的有害病原体的有效防御,同时保持免疫稳态,以避免对无害食物和共生抗原产生过度的免疫反应,这些是乳糜泻和炎症性肠病(IBD)等炎症性疾病的重要原因。在整个胃肠道的多种细胞类型中都检测到了各种离子通道。通过调节膜特性和细胞内生化信号,离子通道在肠道中不同细胞成分的同步信号传递中发挥着关键作用,从而协调胃肠道的免疫反应。这项工作重点关注离子通道在免疫细胞、非免疫常驻细胞和神经免疫相互作用中的作用,包括在稳态和病理条件下的作用。了解这些免疫相关途径中离子通道信号的细胞和分子基础,并初步测试药理学干预,将有助于开发基于离子通道的治疗方法,以治疗肠道炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/566e/9723512/9314290c04ad/JGP_202113042_Fig1.jpg

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