Defective IgA response to atypical intestinal commensals in IL-21 receptor deficiency reshapes immune cell homeostasis and mucosal immunity.
Defective IgA response to atypical intestinal commensals in IL-21 receptor deficiency reshapes immune cell homeostasis and mucosal immunity.
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DOI：
10.1038/s41385-018-0056-x
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发表时间：
2019-01
影响因子：
8
通讯作者：
Kelsall BL
中科院分区：
文献类型：
--
作者：
Cho H;Jaime H;de Oliveira RP;Kang B;Spolski R;Vaziri T;Myers TG;Thovarai V;Shen Z;Fox JG;Leonard WJ;Kelsall BL
尽管研究表明IL-21信号在肠道炎症中的作用，但其在肠道内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区系对IL-21受体缺陷的表型表现的潜在影响。IL-21在小肠中大量产生，似乎是针对节段性丝状细菌和螺杆菌等非典型共生体的IgA反应的关键，但对大多数共生体不起作用。在这些非典型共生体的存在下，IL-21R缺陷小鼠的生发中心和IgA+B细胞数量减少，Peyer‘s斑块中活化诱导的胞苷脱氨酶表达减少，小肠IgA+浆母细胞和浆细胞显著减少，导致更高的细菌负荷和Th17和Treg细胞的随后扩张。这些微生物区系介导的继发性变化反过来增强T细胞对口服抗原的反应，并显著抑制轮状柠檬酸杆菌诱导的免疫病理，表明IL-21介导的粘膜免疫、微生物区系和病原体之间存在复杂的相互作用。
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.
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影响因子：
32.4
作者：
Basu R;O'Quinn DB;Silberger DJ;Schoeb TR;Fouser L;Ouyang W;Hatton RD;Weaver CT
通讯作者：
Weaver CT
影响因子：
32.4
作者：
Bunker JJ;Flynn TM;Koval JC;Shaw DG;Meisel M;McDonald BD;Ishizuka IE;Dent AL;Wilson PC;Jabri B;Antonopoulos DA;Bendelac A
通讯作者：
Bendelac A
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
影响因子：
29.4
作者：
Fina, Daniele;Sarra, Massimiliano;Monteleone, Giovanni
通讯作者：
Monteleone, Giovanni
影响因子：
20.3
作者：
Attridge, Kesley;Wang, Chun Jing;Walker, Lucy S. K.
通讯作者：
Walker, Lucy S. K.