Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
Am J Pathol. 2011 Feb;178(2):735-43. doi: 10.1016/j.ajpath.2010.10.022.
B cells mediate multiple functions that influence immune and inflammatory responses. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to immediate intestinal injury. Dextran sulfate sodium-induced intestinal injury serves as an experimental animal model for human ulcerative colitis. The contribution of B cells to DSS-induced intestinal injury is unclear. In this study, we show that DSS-induced intestinal injury was more severe in CD19-deficient (CD19(-/-)) mice than in wild-type mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1% to 2% of splenic B220(+) cells in wild-type mice. Remarkably, adoptive transfer of these B10 cells from wild-type mice reduced inflammation in CD19(-/-) mice in an IL-10-dependent manner. These results demonstrate that IL-10 production from regulatory B10 cells regulates DSS-induced intestinal injury. These findings may provide new insights and therapeutic approaches for treating ulcerative colitis.
B 细胞介导多种功能，影响免疫和炎症反应。在小鼠中，将葡聚糖硫酸钠（DSS）添加到饮用水中会导致立即的肠道损伤。葡聚糖硫酸钠诱导的肠道损伤是人类溃疡性结肠炎的实验动物模型。B 细胞对 DSS 诱导的肠道损伤的贡献尚不清楚。在这项研究中，我们表明，CD19 缺陷（CD19(-/-)）小鼠的 DSS 诱导的肠道损伤比野生型小鼠更严重。这些炎症反应受到独特的 IL-10 产生 CD1d(hi)CD5(+)调节性 B 细胞亚群（B10 细胞）的负调节，该亚群在 CD19(-/-)小鼠中缺失，并且仅占野生型小鼠脾 B220(+)细胞的 1%至 2%。值得注意的是，从野生型小鼠中过继转移这些 B10 细胞以依赖于 IL-10 的方式减少了 CD19(-/-)小鼠中的炎症。这些结果表明，调节性 B10 细胞的 IL-10 产生调节 DSS 诱导的肠道损伤。这些发现可能为治疗溃疡性结肠炎提供新的见解和治疗方法。
