E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis.
E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis.
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DOI：
10.1016/j.immuni.2010.03.017
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发表时间：
2010-04-23
期刊：
影响因子：
32.4
通讯作者：
Powrie F
中科院分区：
文献类型：
--
作者：
Siddiqui KR;Laffont S;Powrie F
树突状细胞（dc）在控制肠道耐受和免疫之间的平衡中起着关键作用。肠道条件CD103+ dc促进调节性T （Treg）细胞反应；然而，人们对驱动肠道炎症的dc知之甚少。在这里，我们发现单核细胞来源的炎性dc表达E-cadherin （CD103的受体），促进肠道炎症。E-cadherin+ dc聚集在炎症的肠系膜淋巴结和结肠中，toll样受体高表达，激活后产生IL-6、IL-23等结肠炎细胞因子。重要的是，E-cadherin+ dc过继转移到T细胞修复的免疫缺陷宿主中，增加了肠道中Th17细胞的反应，导致结肠炎加重。这些结果确定了与肠道炎症发病机制相关的单核细胞来源的炎症性DC亚群，为炎症性肠病的治疗提供了治疗靶点。►E-cadherin+ dc积聚在炎症的MLN和结肠中►E-cadherin+ dc主要来源于Gr1+炎性单核细胞►E-cadherin+ dc产生大量炎性细胞因子和趋化因子►E-cadherin+ dc加重结肠炎
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. ► E-cadherin+ DCs accumulate in the inflamed MLN and colon ► E-cadherin+ DCs derive mainly from Gr1+ inflammatory monocytes ► E-cadherin+ DCs produce high amounts of inflammatory cytokines and chemokines ► E-cadherin+ DCs exacerbate colitis
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