Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Autoimmun Rev. 2021 Apr;20(4):102777. doi: 10.1016/j.autrev.2021.102777. Epub 2021 Feb 17.
Under homeostatic conditions, bidirectional interactions between the gastrointestinal and the immune system allow production of both inflammatory and anti-inflammatory responses designed to prevent undesirable inflammation and to respond efficiently to potential insults. This balanced regulation can be disrupted in disorders that affect tissues remote to the gastrointestinal tract, as seen in autoimmune diseases. Recent reports have described a variety of B lymphocyte-mediated functions that likely contribute to gastrointestinal homeostasis to a greater extent than previously thought. Studies have shown that early B cell development takes place within the intestine, and that self-reactive B cells are rendered tolerant using mechanisms known to occur in the bone marrow, indicating that the gastrointestinal tract contributes to maintaining immune tolerance to self. Relatedly, continuous bacterial stimulation is essential for maintaining regulatory B cell functions and for mediating mucosal homeostasis. In studies of neuro-inflammation, intestinal IgA+ B cells, which constitute a prominent source of lymphocytes in the organism, can migrate to inflamed tissues and exert regulatory functions that attenuate inflammation in the central nervous system, indicating that, in addition to its local effects in the intestin, gut microbiota-B cell crosstalk can exert long-range beneficial effects. At the translational level, metabolites produced by gut microbiota can act as B cell-intrinsic epigenetic modulators, reducing inflammation in the skin and kidneys of mice suffering from experimental lupus. Given the significant impact of B cell-intestinal microbiota interactions, there is a momentum for improving our understanding of these pathways in autoinflammatory diseases and for designing novel therapeutic strategies for systemic autoimmune diseases where B cells play key roles.
在稳态条件下，胃肠道和免疫系统之间的双向相互作用允许产生炎症和抗炎反应，旨在防止不希望的炎症，并有效地应对潜在的损伤。这种平衡调节可以在影响胃肠道以外组织的疾病中被破坏，如自身免疫性疾病。最近的报告描述了多种 B 淋巴细胞介导的功能，这些功能可能比以前认为的更有助于胃肠道的稳态。研究表明，早期 B 细胞发育发生在肠道内，并且使用已知发生在骨髓中的机制使自身反应性 B 细胞耐受，这表明胃肠道有助于维持对自身的免疫耐受。相关地，持续的细菌刺激对于维持调节性 B 细胞功能和介导粘膜稳态是必需的。在神经炎症研究中，肠道 IgA+B 细胞是机体中淋巴细胞的主要来源，它们可以迁移到炎症组织并发挥调节作用，减轻中枢神经系统的炎症，这表明，除了在肠道中的局部作用外，肠道菌群-B 细胞相互作用还可以发挥远程有益作用。在转化水平上，肠道菌群产生的代谢产物可以作为 B 细胞内在的表观遗传调节剂，减少患有实验性狼疮的小鼠的皮肤和肾脏炎症。鉴于 B 细胞-肠道菌群相互作用的重大影响，人们正在努力提高对自身炎症性疾病中这些途径的理解，并为 B 细胞发挥关键作用的系统性自身免疫性疾病设计新的治疗策略。
