RIKEN Research Center for Allergy Immunology, Yokohama, Japan.
Annu Rev Immunol. 2010;28:243-73. doi: 10.1146/annurev-immunol-030409-101314.
In mammals, the gastrointestinal tract harbors an extraordinarily dense and complex community of microorganisms. The gut microbiota provide strong selective pressure to the host to evolve adaptive immune responses required for the maintenance of local and systemic homeostasis. The continuous antigenic presence in the gut imposes a dynamic remodeling of gut-associated lymphoid tissues (GALT) and the selection of multiple layered strategies for immunoglobulin (Ig) A production. The composite and dynamic gut environment also necessitates heterogeneous, versatile, and convertible T cells, capable of inhibiting (Foxp3(+) T cells) or helping (T(FH) cells) local immune responses. In this review, we describe recent advances in our understanding of dynamic pathways that lead to IgA synthesis, in gut follicular structures and in extrafollicular sites, by T cell-dependent and T cell-independent mechanisms. We discuss the finely tuned regulatory mechanisms for IgA production and emphasize the role of mucosal IgA in the selection and maintenance of the appropriate microbial composition that is necessary for immune homeostasis.
在哺乳动物中，胃肠道中栖息着极其密集和复杂的微生物群落。肠道微生物群对宿主施加了强大的选择压力，促使宿主进化出适应性免疫反应，以维持局部和全身的稳态。肠道中持续存在的抗原会导致肠道相关淋巴组织（GALT）发生动态重塑，并选择多种 IgA 产生的分层策略。复杂和动态的肠道环境还需要具有异质性、多功能和可转换性的 T 细胞，这些细胞能够抑制（Foxp3(+) T 细胞）或辅助（T(FH) 细胞）局部免疫反应。在这篇综述中，我们描述了我们对 IgA 合成的动态途径的最新理解，这些途径通过 T 细胞依赖性和非依赖性机制在肠道滤泡结构和滤泡外部位发生。我们讨论了 IgA 产生的精细调控机制，并强调了黏膜 IgA 在选择和维持适当微生物组成中的作用，这对于免疫稳态是必要的。
