State Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Cell Biology and Immunology Group, Wageningen University and Research, Wageningen, The Netherlands.
Eur J Immunol. 2024 Oct;54(10):e2350704. doi: 10.1002/eji.202350704. Epub 2024 Jul 7.
Secretory IgA is crucial for preventing the invasion of entero-pathogens via intestinal mucosa. While it is well-established that Transforming growth factor β1 (TGF-β1) regulates IgA production in human and mouse B cells, our previous investigation revealed different functions of TGF-β1 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-β1 to evaluate the effect of TGF-β1 on pigs. The results showed that antibody production from B cells of PPs was impaired by TGF-β1 ex vivo. Furthermore, TGF-β1 treatment led to a decrease in the expression of germ-line transcript αand postswitch transcript α. Moreover, we observed that TGF-β1 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-β1 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-β1-mediated inhibition of B-cell activation.
分泌型免疫球蛋白 A（Secretory IgA）对于防止肠病原体通过肠黏膜的入侵至关重要。虽然已经证实转化生长因子 β1（Transforming growth factor β1，TGF-β1）可调节人类和小鼠 B 细胞中的 IgA 产生，但我们之前的研究表明，TGF-β1 在猪的 IgA 产生中的功能与人类和小鼠不同，其潜在机制尚不清楚。在本研究中，我们从猪派尔集合淋巴结（Peyer's patches，PPs）中分离出 IgM B 细胞，并使用重组猪 TGF-β1 刺激它们，以评估 TGF-β1 对猪的影响。结果表明，TGF-β1 在体外会损害 PPs B 细胞的抗体产生。此外，TGF-β1 处理导致种系转录本 α 和开关后转录本 α 的表达减少。此外，我们观察到 TGF-β1 主要抑制丝裂原活化蛋白激酶（mitogen-activated protein kinases，MAPK）的 p38 磷酸化，证实了 p38-MAPK 途径参与了猪 IgA 的产生和 IgA 类别转换重组。应用 p38-MAPK 抑制剂会导致 B 细胞分化水平降低。总之，本研究表明，外源性 TGF-β1 通过抑制猪 PPs B 细胞中的 p38-MAPK 信号转导来抑制 IgA 抗体的产生和类别转换重组，这可能构成 TGF-β1 介导的 B 细胞激活抑制的一部分。
