New Therapy with CXCL16 Blocking for Inflammatory Bowel Disease

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(Background &Aim) CXCL16 is selectively expressed on only APC such as dendritic cells and macrophages. CXCL16 supports binding and phagocytosis of both gram-positive and negative bacteria through the chemokine-domain, suggesting that it may be involved in facilitating uptake of various pathogens and APC-T cell interactions in initiation of immune response. In this regard, it may be interesting to speculate that the interaction between APC and T cells through CXCL16 in response to various stimuli such as luminal bacteria components is involved in the pathophysiology of IBD. Therefore, the aim of the present study is to examine whether or not regulation of CXCL16 is effective for inflammatory bowel disease. (Methods) We generate CXCL16 knock out mice and anti-CXCL16mAbIgG1 and anti-human CXCL16mAbs. Induction of Colitis: To induce colitis, C57BL/6 mice are given 3%DSS (mol wt, 36-50 kilodaltons) in their drinking water for 5 days (from day 0 to 4). TNBS colitis is induced in SJL/J mice by using a modification of the method described by Neurath et. Al. Clinical evaluation after treatment by anti-CXCL16mAb: After induction of colitis, mice are injected with 500μg anti-CXCL16mAb or control rat IgG. For 5 days. (Results) Administration of anti-CXCL16 antibody dramatically decreased the severity of colonic inflammation in both DSS and TNBS colitis models. Production of both TNF-α and IFN-γ from mesenteric lymph node cells will be significantly lower in the group treated with anti-CXCL16 antibody than in non-treated group. The number of lymphocytes of CD4^+ CD69^+ T cells from the MLN in the mice treated with anti-CXCL16 was significantly lower than those in non-treated group. These finding suggested that CXCL16 is one of the most important chemokines, which is involved in the intestinal inflammation. (Conclusion) This data demonstrate the first evidence that dysregulation of CXCL16 activity is one of the important pathogenetic factor for human IBD.