IL-10-Producing Regulatory B10 Cells Inhibit Intestinal Injury in a Mouse Model
IL-10-Producing Regulatory B10 Cells Inhibit Intestinal Injury in a Mouse Model
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DOI：
10.1016/j.ajpath.2010.10.022
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发表时间：
2011-02-01
影响因子：
6
通讯作者：
Sato, Shinichi
中科院分区：
文献类型：
--
作者：
Yanaba, Koichi;Yoshizaki, Ayumi;Sato, Shinichi
B细胞介导影响免疫和炎症反应的多种功能。在小鼠中，向饮用水中添加葡聚糖硫酸钠（DSS）会导致立即的肠道损伤。葡聚糖硫酸钠诱导的肠损伤可作为人类溃疡性结肠炎的实验动物模型。B细胞在DSS诱导的肠损伤中的作用尚不清楚。在这项研究中，我们发现DSS诱导的肠道损伤在CD 19缺陷（CD 19（-/-））小鼠中比野生型小鼠更严重。这些炎症反应受到一种独特的产生IL-10的CD 1d（hl）CD 5（+）调节性B细胞亚群（B10细胞）的负调控，该亚群在CD 19（-/-）小鼠中不存在，在野生型小鼠中仅占脾B220（+）细胞的1%至2%。值得注意的是，这些来自野生型小鼠的B10细胞的过继转移以IL-10依赖性方式减少了CD 19（-/-）小鼠的炎症。这些结果表明，从调节B10细胞产生的IL-10调节DSS诱导的肠损伤。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。(Am J Pathol 2011，178：735-743; 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(hl)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. (Am J Pathol 2011, 178:735-743; DOI: 10.1016/j.ajpath.2010.10.022)