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TGF-β1 impairs IgA class switch recombination and production in porcine Peyer's patches B cells

文献类型： 外文期刊

作者： Wang, Caiying;Zhang, Yue;Lu, Yabin;Huang, Xin;Jiang, Huazheng;Chen, Guohui;Shao, Yongheng;Savelkoul, Huub F. J.;Jansen, Christine A.;Liu, Guangliang

作者机构：

关键词： IgA;IgM(+) B cells;p38-MAPK;Peyer's patches;TGF-beta 1

期刊名称： EUROPEAN JOURNAL OF IMMUNOLOGY

ISSN： 0014-2980

年卷期： 2024 年

页码：

收录情况： SCIE（2024版）

摘要： Secretory IgA is crucial for preventing the invasion of entero-pathogens via intestinal mucosa. While it is well-established that Transforming growth factor beta 1 (TGF-beta 1) regulates IgA production in human and mouse B cells, our previous investigation revealed different functions of TGF-beta 1 in IgA generation in pigs compared with humans and mice, with the underlying mechanism remaining elusive. In this study, IgM+ B cells from porcine Peyer's patches (PPs) were isolated and stimulated with recombinant porcine TGF-beta 1 to evaluate the effect of TGF-beta 1 on pigs. The results showed that antibody production from B cells of PPs was impaired by TGF-beta 1 ex vivo. Furthermore, TGF-beta 1 treatment led to a decrease in the expression of germ-line transcript alpha and postswitch transcript alpha. Moreover, we observed that TGF-beta 1 predominantly inhibited the phosphorylation of p38-mitogen-activated protein kinases (MAPK), confirming the involvement of the p38-MAPK pathway in porcine IgA generation and IgA class switch recombination. The application of p38-MAPK inhibitor resulted in decreased B-cell differentiation levels. Collectively, this study demonstrates that exogenous TGF-beta 1 restrains the production and class switch recombination of IgA antibodies by inhibiting p38-MAPK signaling in porcine PPs B cells, which may constitute a component of TGF-beta 1-mediated inhibition of B-cell activation.

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