Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.
Manchester Collaborative Centre for Inflammation Research, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
J Exp Med. 2019 Apr 1;216(4):728-742. doi: 10.1084/jem.20180871. Epub 2019 Feb 27.
Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell-dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell-dependent IgA responses remain incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3) regulate steady state interactions between T follicular helper cells (TfH) and B cells to limit mucosal IgA responses. ILC3 used conserved migratory cues to establish residence within the interfollicular regions of the intestinal draining lymph nodes, where they act to limit TfH responses and B cell class switching through antigen presentation. The absence of ILC3-intrinsic antigen presentation resulted in increased and selective IgA coating of bacteria residing within the colonic mucosa. Together these findings implicate lymph node resident, antigen-presenting ILC3 as a critical regulatory checkpoint in the generation of T cell-dependent colonic IgA and suggest ILC3 act to maintain tissue homeostasis and mutualism with the mucosal-dwelling commensal microbiota.
肠道免疫稳态依赖于宿主与共生菌群之间受到严格调控和动态变化的相互作用。黏膜 B 细胞产生的免疫球蛋白 A（IgA）决定了肠道内共生菌的组成。虽然有新的证据表明，大部分 IgA 是先天产生的，可能具有多反应性，但黏膜栖息的物种也可以通过 T 细胞依赖性机制诱导 IgA 产生。然而，调节 T 细胞依赖性 IgA 反应的幅度和质量的机制仍不完全清楚。在这里，我们证明了第 3 组先天淋巴样细胞（ILC3）调节滤泡辅助性 T 细胞（Tfh）和 B 细胞之间的稳态相互作用，以限制黏膜 IgA 反应。ILC3 使用保守的迁移线索在肠引流淋巴结的滤泡间区域建立居留，在那里它们通过抗原呈递来限制 Tfh 反应和 B 细胞类别转换。ILC3 内在的抗原呈递缺失导致结肠黏膜内驻留的细菌上 IgA 选择性增加和覆盖。这些发现共同表明，淋巴结驻留的抗原呈递 ILC3 是 T 细胞依赖性结肠 IgA 产生的一个关键调节检查点，并表明 ILC3 作用是维持组织内稳态和与黏膜共生菌群的共生关系。
