Elucidation of the regulatory mechanisms for mucosal immune response by mucosal IL-7/IL-7 receptor system

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Our group has been focusing on the fundamental roles of intestinal epithelial cell-derived IL-7 and IL-7R-expressing lymphoid cells in local immune regulation within the gut. In this project, further attempts were made 1) to elucidate the regulatory mechanisms of IL-7 production in intestinal epithe-hal cells, and 2) to test whether elimination of IL-7R-expressing cells by toxin-conjugated anti-IL-7R antibodies might influence the pathogenesis of chronic colitis. We showed 1) that gene expression and protein production of JL-7 in intestinal epithelial cells are elegantly regulated by IRF family of tran-scription factors and also 2) that direct immunotoxin targeting of IL-7R caused significant ameliora-tion of chronic colitis in several model mice. These results not only provide a better understanding of the molecular mechanisms of mucosal immune regulation, but also propose the mucosal IL-7/IL-7R system to be a potential therapeutic target for a certain type of chronic colitis in humans.