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

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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.