T helper type 1 memory cells disseminate postoperative ileus over the entire intestinal tract
T helper type 1 memory cells disseminate postoperative ileus over the entire intestinal tract
复制标题
DOI：
10.1038/nm.2255
复制
发表时间：
2010-12-01
期刊：
影响因子：
82.9
通讯作者：
Kurts, Christian
中科院分区：
文献类型：
--
作者：
Engel, Daniel R.;Koscielny, Arne;Kurts, Christian
局部腹部手术可导致整个胃肠道动力障碍(术后肠梗阻)。肠道巨噬细胞产生使肌细胞瘫痪的介质，但目前尚不清楚巨噬细胞是如何激活的，特别是那些未经处理的肠道区域的巨噬细胞。在这里，我们显示肠道手术激活肠道CD103(+)、CD11b(+)树突状细胞(DC)来产生白介素12(IL-12)。这促进了CCR9(+)记忆T辅助1型(T(H)1)细胞分泌干扰素-γ，从而激活巨噬细胞。IL-12还导致一些T(H)1细胞从手术处理过的部位通过血流迁移到未处理的肠道区域，在那里它们会导致肠梗阻。用药物FTY720预防T细胞迁移或抑制IL-12、T-bet(T(H)1特异性T盒转录因子)或干扰素-γ可预防术后肠梗阻。腹部手术后1h静脉血中检测到CCR9(+)T(H)1记忆细胞。这些发现表明术后肠梗阻是一种T(H)1免疫介导的疾病，并确定了疾病监测和治疗的潜在靶点。(C)2010自然美国公司。保留所有权利。
Localized abdominal surgery can lead to disruption of motility in the entire gastrointestinal tract (postoperative ileus). Intestinal macrophages produce mediators that paralyze myocytes, but it is unclear how the macrophages are activated, especially those in unmanipulated intestinal areas. Here we show that intestinal surgery activates intestinal CD103(+) CD11b(+) dendritic cells (DCs) to produce interleukin-12 (IL-12). This promotes interferon-gamma(IFN-gamma) secretion by CCR9(+) memory T helper type 1 (T(H)1) cells which activates the macrophages. IL-12 also caused some T(H)1 cells to migrate from surgically manipulated sites through the bloodstream to unmanipulated intestinal areas where they induced ileus. Preventing T cell migration with the drug FTY720 or inhibition of IL-12, T-bet (T(H)1-specific T box transcription factor) or IFN-gamma prevented postoperative ileus. CCR9(+) T(H)1 memory cells were detected in the venous blood of subjects 1 h after abdominal surgery. These findings indicate that postoperative ileus is a T(H)1 immune-mediated disease and identify potential targets for disease monitoring and therapy. (C) 2010 Nature America, Inc. All rights reserved.