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醋酸盐差异调节 IgA 对共生细菌的反应性
2021-07-18 14:38

日本 RIKEN 综合医学科学中心Hiroshi Ohno研究团队发现醋酸盐差异调节免疫球蛋白 A (IgA) 对共生细菌的反应性。2021年7月14日出版的《自然》杂志发表了这项成果。

他们表明醋酸盐——一种主要的肠道微生物代谢物——不仅增加了结肠中 IgA 的产生,而且还改变了 IgA 池与特定微生物(包括肠杆菌)结合的能力。在属于肠杆菌属的大肠杆菌单克隆化的小鼠中观察到醋酸诱导共生反应性 IgA 和 IgA 库的变化,但没有观察到主要共生拟杆菌 thetaiotaomicron,这表明醋酸指导选择性 IgA 结合某些微生物。从机制上讲,醋酸盐协调上皮细胞和免疫细胞之间的相互作用,诱导微生物刺激的 CD4 T 细胞以支持 T 细胞依赖性 IgA 的产生,并因此改变了这些细菌在结肠内的定位。总的来说,他们确定了肠道微生物代谢物在调节差异 IgA 产生以维持粘膜稳态中的作用。

据悉,细菌定植与其在肠道中的封闭之间的平衡对于人类与其细菌之间的共生关系是必不可少的。维持粘膜表面稳态的一种成分是IgA,它是哺乳动物中含量最丰富的免疫球蛋白。多项研究揭示了多反应性 IgA 的重要特征,它是在没有共生细菌的情况下自然产生的。然而,考虑到肠道环境中的动态变化,共生反应性 IgA 库是如何形成的,以及这种 IgA 如何影响微生物群落,仍然不确定。

附:英文原文

Title: Acetate differentially regulates IgA reactivity to commensal bacteria

Author: Tadashi Takeuchi, Eiji Miyauchi, Takashi Kanaya, Tamotsu Kato, Yumiko Nakanishi, Takashi Watanabe, Toshimori Kitami, Takashi Taida, Takaharu Sasaki, Hiroki Negishi, Shu Shimamoto, Akinobu Matsuyama, Ikuo Kimura, Ifor R. Williams, Osamu Ohara, Hiroshi Ohno

Issue&Volume: 2021-07-14

Abstract: The balance between bacterial colonization and its containment in the intestine is indispensable for the symbiotic relationship between humans and their bacteria. One component to maintain homeostasis at the mucosal surfaces is immunoglobulin A (IgA), the most abundant immunoglobulin in mammals1,2. Several studies have revealed important characteristics of poly-reactive IgA3,4, which is produced naturally without commensal bacteria. Considering the dynamic changes within the gut environment, however, it remains uncertain how the commensal-reactive IgA pool is shaped and how such IgA affects the microbial community. Here we show that acetate—one of the major gut microbial metabolites—not only increases the production of IgA in the colon, but also alters the capacity of the IgA pool to bind to specific microorganisms including Enterobacterales. Induction of commensal-reactive IgA and changes in the IgA repertoire by acetate were observed in mice monocolonized with Escherichia coli, which belongs to Enterobacterales, but not with the major commensal Bacteroides thetaiotaomicron, which suggests that acetate directs selective IgA binding to certain microorganisms. Mechanistically, acetate orchestrated the interactions between epithelial and immune cells, induced microbially stimulated CD4 T cells to support T-cell-dependent IgA production and, as a consequence, altered the localization of these bacteria within the colon. Collectively, we identified a role for gut microbial metabolites in the regulation of differential IgA production to maintain mucosal homeostasis.

DOI: 10.1038/s41586-021-03727-5

Source: https://www.nature.com/articles/s41586-021-03727-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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