IL-21 Promotes Intestinal Memory IgA Responses.
IL-21 Promotes Intestinal Memory IgA Responses.
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DOI：
10.4049/jimmunol.1900766
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发表时间：
2020-10-01
期刊：
影响因子：
--
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Huang X;Yang W;Yao S;Bilotta AJ;Lu Y;Zhou Z;Kumar P;Dann SM;Cong Y
IL-21主要由辅助性T细胞（Th）17和滤泡辅助性T细胞产生，其在B细胞分化和抗体类别转换中的作用已被深入研究。然而，IL-21如何调节肠道中的记忆伊加+ B细胞发育和记忆伊加应答仍不完全清楚。在这项研究中，我们发现转移微生物群抗原特异性Th 17细胞后，TCRβxδ−/−小鼠肠道固有层（LP）中的总伊加+ B细胞以及CD 38 + CD 138 −伊加+记忆B细胞显著增加，而不是Th 1细胞。尽管IL-21 R −/−小鼠或IL-17 R −/−小鼠在感染啮齿类柠檬酸杆菌后显示出肠道中抗原特异性记忆伊加的产生减少（C.啮齿类），在再次感染C.与WT小鼠比较。阻断IL-21在体内抑制肠C。PP和LP中啮齿类特异性伊加产生以及伊加+CD 38 + CD 138 −记忆B细胞。此外，IL-21在体外显著诱导B细胞伊加产生，并增加与类别转换和记忆B细胞发育相关的基因的表达，包括Aicda、Ski、Bmi 1和Klf 2。一致的是，C.啮齿动物再感染。总之，我们的研究表明，IL-21促进肠道记忆伊加B细胞的发展，可能通过上调分化相关和类转换相关基因，表明IL-21在肠道记忆伊加+ B细胞反应中的潜在作用。
The role of IL-21, produced mainly by T helper (Th) 17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and antibody class switch. However, how IL-21 regulates memory IgA+ B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA+ B cells as well as CD38+CD138−IgA+ memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ−/− mice after transfer of microbiota antigen-specific Th17 cells but not Th1 cells. Although IL-21R−/− mice or IL-17R−/− mice showed decreased antigen-specific memory IgA production in the intestines upon infection with Citrobacter rodentium (C. rodentium), the percentage of IgA+CD38+CD138− memory B cells in Peyer’s patches (PP) and LP was decreased only in IL-21R−/− mice, but not in IL-17R−/− mice, after re-infection with C. rodentium compared with WT mice. Blockade IL-21 in vivo suppressed intestinal C. rodentium-specific IgA production as well as IgA+CD38+CD138− memory B cells in PP and LP. Furthermore, IL-21 significantly induced B cell IgA production in vitro, with the increased expression of genes related with class-switching and memory B cell development, including Aicda, Ski, Bmi1, and Klf2. Consistently, Acida and Ski expression was decreased in B cells of IL-21R−/− mice after C. rodentium re-infection. In conclusion, our study demonstrated that IL-21 promotes intestinal memory IgA B cell development, possibly through up-regulating differentiation-related and class switching-related genes, indicating a potential role of IL-21 in memory IgA+ B cell responses in the intestines.
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DOI：
10.1084/jem.20092253
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
通讯作者：
Cong Y
影响因子：
3.1
作者：
Dann, Sara M.;Le, Christine;Eckmann, Lars
通讯作者：
Eckmann, Lars
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
影响因子：
4.4
作者：
Good, Kim L.;Bryant, Vanessa L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.
影响因子：
8
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
通讯作者：
Kelsall BL