Laboratory for Intestinal Ecosystem, Center for Integrative Medical Sciences, RIKEN Yokohama, Kanagawa 230-0045, Japan; Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University Yokohama, Kanagawa 230-0045, Japan.
Laboratory for Intestinal Ecosystem, Center for Integrative Medical Sciences, RIKEN Yokohama, Kanagawa 230-0045, Japan; Immunobiology Laboratory, Graduate School of Medical Life Science, Yokohama City University Yokohama, Kanagawa 230-0045, Japan.
Immunity. 2020 Apr 14;52(4):635-649.e4. doi: 10.1016/j.immuni.2020.03.002. Epub 2020 Apr 1.
The intestinal microbiota shapes and directs immune development locally and systemically, but little is known about whether commensal microbes in the stomach can impact their immunological microenvironment. Here, we report that group 2 innate lymphoid cells (ILC2s) were the predominant ILC subset in the stomach and show that their homeostasis and effector functions were regulated by local commensal communities. Microbes elicited interleukin-7 (IL-7) and IL-33 production in the stomach, which in turn triggered the propagation and activation of ILC2. Stomach ILC2s were also rapidly induced following infection with Helicobacter pylori. ILC2-derived IL-5 resulted in the production of IgA, which coated stomach bacteria in both specific pathogen-free (SPF) and H. pylori-infected mice. Our study thus identifies ILC2-dependent IgA response that is regulated by the commensal microbiota, which is implicated in stomach protection by eliminating IgA-coated bacteria including pathogenic H. pylori.
肠道微生物群在局部和全身范围内塑造和指导免疫发育，但对于胃中的共生微生物是否会影响其免疫微环境知之甚少。在这里，我们报告说，2 组先天淋巴细胞（ILC2）是胃中的主要 ILC 亚群，并表明其体内平衡和效应功能受局部共生群落的调节。微生物在胃中引发白细胞介素 7（IL-7）和 IL-33 的产生，进而触发 ILC2 的增殖和激活。感染幽门螺杆菌后，胃 ILC2 也迅速被诱导。ILC2 衍生的 IL-5 导致 IgA 的产生，该 IgA 在无特定病原体（SPF）和 H. pylori 感染的小鼠中均覆盖胃细菌。因此，我们的研究确定了由 ILC2 依赖的 IgA 反应，该反应受共生微生物群的调节，通过消除包括致病性 H. pylori 在内的 IgA 包被细菌，从而参与胃保护。
