Despite studies indicating the effects of IL-21 signaling in intestinal inflammation, its roles in intestinal homeostasis and infection are not yet clear. Here, we report potent effects of commensal microbiota on the phenotypic manifestations of IL-21 receptor deficiency. IL-21 is produced highly in the small intestine and appears to be critical for mounting an IgA response against atypical commensals such as segmented filamentous bacteria and Helicobacter, but not to the majority of commensals. In the presence of these atypical commensals, IL-21R-deficient mice exhibit reduced numbers of germinal center and IgA⁺ B cells and expression of activation-induced cytidine deaminase in Peyer's patches as well as a significant decrease in small intestine IgA⁺ plasmablasts and plasma cells, leading to higher bacterial burdens and subsequent expansion of Th17 and Treg cells. These microbiota-mediated secondary changes in turn enhance T cell responses to an oral antigen and strikingly dampen Citrobacter rodentium-induced immunopathology, demonstrating a complex interplay between IL-21-mediated mucosal immunity, microbiota, and pathogens.

中文翻译：

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IgA 对 IL-21 受体缺陷中非典型肠道共生体的反应缺陷重塑了免疫细胞稳态和粘膜免疫。

尽管研究表明 IL-21 信号在肠道炎症中的作用，但其在肠道稳态和感染中的作用尚不清楚。在这里，我们报告了共生微生物群对 IL-21 受体缺陷表型表现的有效影响。IL-21 在小肠中大量产生，似乎对于针对非典型共生体（如分段丝状细菌和螺杆菌）产生 IgA 反应至关重要，但对大多数共生体而言并非如此。在存在这些非典型共生体的情况下，IL-21R 缺陷小鼠的生发中心和 IgA ⁺ B 细胞数量减少，淋巴集结中活化诱导的胞苷脱氨酶表达减少，小肠 IgA ^{+显着减少}浆母细胞和浆细胞，导致更高的细菌负荷和随后的 Th17 和 Treg 细胞扩增。这些微生物群介导的继发性变化反过来增强了 T 细胞对口服抗原的反应，并显着抑制了柠檬酸杆菌诱导的免疫病理学，证明了 IL-21 介导的粘膜免疫、微生物群和病原体之间复杂的相互作用。