Development of novel therapy targeting dendritic cells for Crohn's disease

克罗恩病（CD）是一种累及胃肠道的慢性炎症过程，其特征为不连续和透壁炎症。虽然CD的病因尚未完全清楚，但越来越多的证据表明，局部免疫系统的失调在CD的发病机制中至关重要。来自人类和实验鼠结肠炎模型的研究表明，在CD中，局部免疫应答倾向于主要是T辅助细胞1型（Th 1），并通过局部释放细胞因子（如肿瘤坏死因子（TNF）-□、白细胞介素（IL）-12和IL-18）反映。然而，还没有阐明是什么触发CD中的Th 1免疫应答。本研究采用密度梯度离心、免疫磁珠法去除CD 3 ^+、CD 11b ^+和CD 16 ^+细胞，再用CD 4 ^+细胞进行阳性分离，建立了从人CD肠系膜淋巴结（MLN）中分离纯化树突状细胞的方法，并对MLN中的免疫级联反应进行了分析。从MLN获得的细胞的分析显示，DC 1的比例增加，在MLN的CD相比，溃疡性结肠炎和控制和CD的MLN的CD 4 + T淋巴细胞显示Th 1 profile.This是第一个研究报告MLN树突状细胞和MLN的CD 4 + T细胞的细胞因子谱从人类IBD患者的表征。本研究表明MLN树突状细胞在IBD的发病机制中具有重要作用。MLN可能是失调的免疫应答（如CD中的Th 1）首先发生的地方。

Crohn's disease(CD) is a chronic inflammatory process involving the gastrointestinal tract, characterised by discontinuous and transmural inflammation. Although the etiology of CD is not fully understood, accumulating evidence suggests that dysregulation of the local immune system is pivotal in the pathogenesis of CD. Studies from humans and experimental murine colitis models indicate that in CD, the local immune response tends to be predominantly T helper cell type 1(Th1) and is reflected by local release of cytokines such as tumor necrosis factor (TNF)-□, interleukin (IL)-12, and IL-18. However, it has not been elucidated what triggers the Th1 immune response in CD. In the present study, we attempted to establish the purification of dendrtic cells from mesenteric lymph nodes(MLN) and to analyze the immune cascade in the mesenteric lymph nodes of human CD.We established the purification of dendrtic cells from MLN by density gradient centrifugation and immunomagnetic depletion of CD3^+,CD11b^+ and CD16^+ cells followed by positive isolation with CD4^+. The analysis of cells obtained from MLNs revealed that the proportion of DC1 was increased in the MLN of CD compared to ulcerative colitis and control and that CD4+ T lymphocytes from the MLN of CD show a Th1 profile.This is the first study to report the characterization of MLN dendritic cells and cytokine profiles of the MLN CD4+ T cells from human IBD patients. This study shows that MLN dendritic cells have considerable effects in the pathogenesis of IBD. The MLN may be the place where the dysregulated immune responses, such as Th1 in CD, first occur.