State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Front Immunol. 2020 Jun 23;11:1303. doi: 10.3389/fimmu.2020.01303. eCollection 2020.
Secretory IgA is critical to prevent the invasion of pathogens via mucosa. However, the key factors and the mechanisms of IgA generation in the porcine gut are not well-understood. In this study, a panel of factors, including BAFF, APRIL, CD40L, TGF-β1, IL-6, IL-10, IL-17A, and IL-21, were employed to stimulate IgM B lymphocytes from porcine ileum Peyer's patches. The results showed that IL-21 significantly upregulated IgA production of B cells and facilitated cell proliferation and differentiation of antibody-secreting cells. In addition, three transcripts in porcine IgA class switch recombination (CSR), germ-line transcript α, post-switch transcript α, and circle transcript α, were first amplified by (nest-)PCR and sequenced. All these key indicators of IgA CSR were upregulated by IL-21 treatment. Furthermore, we found that IL-21 predominantly activated JAK1, STAT1, and STAT3 proteins and confirmed that the JAK-STAT signaling pathway was involved in porcine IgA CSR. Thus, IL-21 plays an important role in the proliferation and differentiation of IgA-secreting cells in porcine Peyer's patches through the JAK-STAT signaling pathway. These findings provide insights into the mucosal vaccine design by regulation of IL-21 for the prevention and control of enteric pathogens in the pig industry.
分泌型免疫球蛋白 A（Secretory IgA）对于防止病原体通过黏膜入侵至关重要。然而，猪肠道中 IgA 产生的关键因素和机制尚不清楚。在本研究中，我们采用了一组因子，包括 BAFF、APRIL、CD40L、TGF-β1、IL-6、IL-10、IL-17A 和 IL-21，来刺激来自猪回肠派尔集合淋巴结的 IgM B 淋巴细胞。结果表明，IL-21 可显著上调 B 细胞的 IgA 产生，并促进抗体分泌细胞的增殖和分化。此外，我们首次通过（巢式）PCR 扩增和测序，得到了猪 IgA 类别转换重组（CSR）中的三个转录本，即种系转录本α、转换后转录本α和环状转录本α。IL-21 处理可上调所有这些 IgA CSR 的关键指标。此外，我们发现 IL-21 主要激活 JAK1、STAT1 和 STAT3 蛋白，并证实 JAK-STAT 信号通路参与了猪 IgA CSR。因此，IL-21 通过 JAK-STAT 信号通路在猪派尔集合淋巴结中 IgA 分泌细胞的增殖和分化中发挥重要作用。这些发现为通过调节 IL-21 设计黏膜疫苗以预防和控制猪肠道病原体提供了新的思路。
