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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 1 ; Zhang, Yue 1 ; Lu, Yabin 4 ; Huang, Xin 1 ; Jiang, Huazheng 1 ; Chen, Guohui 1 ; Shao, Yongheng 1 ; Savelkoul, Huub F. J. 3 ; Jansen, Christine A. 3 ; Liu, Guangliang 1 ;

作者机构: 1.Lanzhou Univ, State Key Lab Anim Dis Control & Prevent, Coll Vet Med, Lanzhou, Peoples R China

2.Chinese Acad Agr Sci, Lanzhou Vet Res Inst, Lanzhou, Peoples R China

3.Wageningen Univ & Res, Cell Biol & Immunol Grp, Wageningen, Netherlands

4.Xinjiang Agr Univ, Coll Vet Med, Urumqi, Peoples R China

5.Hainan Acad Agr Sci, Inst Anim Husb & Vet Med, Hainan Key Lab Trop Anim Breeding & Infect Dis Re, Haikou, Hainan, Peoples R China

6.Gansu Prov Res Ctr Basic Disciplines Pathogen Bio, Lanzhou, Peoples R China

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

期刊名称:EUROPEAN JOURNAL OF IMMUNOLOGY ( 影响因子:4.5; 五年影响因子:4.6 )

ISSN: 0014-2980

年卷期: 2024 年

页码:

收录情况: SCI

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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