Abstract:
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.
摘要:
分泌型IgA对于防止肠病原体通过肠粘膜侵入至关重要。虽然已经确定转化生长因子β1(TGF-β1)调节人和小鼠B细胞中IgA的产生,我们之前的研究揭示了TGF-β1在猪IgA生成中的不同功能,与人和小鼠相比,潜在的机制仍然难以捉摸。在这项研究中,从猪Peyer's斑块(PPs)中分离IgMB细胞,并用重组猪TGF-β1刺激以评估TGF-β1对猪的作用。结果表明,体外TGF-β1损害了PPsB细胞的抗体产生。此外,TGF-β1处理导致种系转录物α和转换后转录物α的表达降低。此外,我们观察到TGF-β1主要抑制p38丝裂原活化蛋白激酶(MAPK)的磷酸化,证实p38-MAPK通路参与猪IgA生成和IgA类开关重组。p38-MAPK抑制剂的应用导致B细胞分化水平降低。总的来说,这项研究表明,外源性TGF-β1通过抑制猪PPsB细胞中的p38-MAPK信号传导来抑制IgA抗体的产生和类别转换重组,可能构成TGF-β1介导的B细胞活化抑制的组成部分。