Sir William Dunn School of Pathology, University of Oxford, OX1 3RE Oxford, UK.
Immunity. 2010 Apr 23;32(4):557-67. doi: 10.1016/j.immuni.2010.03.017. Epub 2010 Apr 15.
Dendritic cells (DCs) play a pivotal role in controlling the balance between tolerance and immunity in the intestine. Gut conditioned CD103(+) DCs promote regulatory T (Treg) cell responses; however, little is known about DCs that drive inflammation in the intestine. Here, we show that monocyte-derived inflammatory DCs that express E-cadherin, the receptor for CD103, promote intestinal inflammation. E-cadherin(+) DCs accumulated in the inflamed mesenteric lymph nodes and colon, had high expression of toll-like receptors, and produced colitogenic cytokines, such as IL-6 and IL-23, after activation. Importantly, adoptive transfer of E-cadherin(+) DCs into T cell-restored immunodeficient hosts increased Th17 cell responses in the intestine and led to exacerbation of colitis. These results identify a monocyte-derived inflammatory DC subset that is associated with the pathogenesis of intestinal inflammation, providing a therapeutic target for the treatment of inflammatory bowel disease.
树突状细胞（DCs）在控制肠道中耐受和免疫之间的平衡方面发挥着关键作用。肠道条件性 CD103(+) DCs 促进调节性 T (Treg) 细胞反应；然而，对于驱动肠道炎症的 DCs 知之甚少。在这里，我们表明表达 E-钙黏蛋白（CD103 的受体）的单核细胞衍生的炎性 DCs 促进肠道炎症。E-钙黏蛋白(+) DCs 在炎症性肠系膜淋巴结和结肠中积累，在激活后高表达 Toll 样受体，并产生致结肠炎细胞因子，如 IL-6 和 IL-23。重要的是，将 E-钙黏蛋白(+) DCs 过继转移到 T 细胞恢复的免疫缺陷宿主中，增加了肠道中的 Th17 细胞反应，并导致结肠炎加重。这些结果鉴定出一种与肠道炎症发病机制相关的单核细胞衍生的炎性 DC 亚群，为治疗炎症性肠病提供了治疗靶点。
