Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, 100850, China.
Cell Mol Immunol. 2019 Jun;16(6):580-589. doi: 10.1038/s41423-018-0041-z. Epub 2018 May 29.
Regulatory B cells (Bregs) are a functionally defined B cell subset, and IL-10 is crucial for the suppressive functions of Bregs. However, little is known regarding how IL-10 production is regulated in B cells. To explore the mechanisms by which IL-10 is regulated in B cells, we used mRNA microarrays to screen for molecules that are upregulated in IL-10-producing B cells and identified RNA-binding motif protein 47 (Rbm47) as a post-transcriptional regulator. Rbm47 was found to promote IL-10 production in B cells. We found that Rbm47 promotes the stability of IL-10 mRNA by binding to AU-rich elements in the 3' untranslated region of Il10 mRNA. In addition, we demonstrated that the overexpression of Rbm47 enabled B cells to facilitate Foxp3 regulator T-cell induction and reduce the severity of DSS-induced ulcerative colitis. Taken together, these results suggest that Rbm47 plays an important role in regulating IL-10 at the post-transcriptional level, thus promoting the regulatory functions of B cells. The findings presented in this study not only increase our understanding of the post-translational regulation of IL-10 in B cells but also identify a novel strategy for the potential application of Bregs.
调节性 B 细胞（Bregs）是一种功能定义明确的 B 细胞亚群，IL-10 对于 Bregs 的抑制功能至关重要。然而，关于 B 细胞中 IL-10 的产生是如何调节的，我们知之甚少。为了探索 B 细胞中 IL-10 调节的机制，我们使用 mRNA 微阵列筛选出在产生 IL-10 的 B 细胞中上调的分子，并鉴定 RNA 结合基序蛋白 47（Rbm47）为一种转录后调节因子。发现 Rbm47 促进 B 细胞中 IL-10 的产生。我们发现 Rbm47 通过结合 Il10 mRNA 3'非翻译区中的富含 AU 元件来促进 IL-10 mRNA 的稳定性。此外，我们证明 Rbm47 的过表达使 B 细胞能够促进 Foxp3 调节性 T 细胞的诱导，并减轻 DSS 诱导的溃疡性结肠炎的严重程度。总之，这些结果表明 Rbm47 在转录后水平上对 IL-10 的调节起着重要作用，从而促进了 B 细胞的调节功能。本研究的结果不仅增加了我们对 B 细胞中 IL-10 的翻译后调节的理解，还为 Bregs 的潜在应用确定了一种新策略。
