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A Novel Therapy for Inflammatory Bowel Disease-Dual Regulatory T-Cell Programming

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Loma Linda University Loma Linda United States

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Inflammatory bowel disease IBD is a group of diseases that are conditions of chronic inflammation in the gastrointestinal tractthe GUT. Current therapies for IBD have a transient effect and are associated with significant side effects due to unintended immune suppression. Hence, a therapy that can lead to a more specific and lasting control of the gut inflammation is urgently needed. This study investigates a novel therapy that aims to induce gut-homing regulatory T Treg cells in the peripheral lymphoid tissues. We propose that the newly generated Treg cells can specifically home to and reinstate immune tolerance in the gut, thereby providing a long-lasting control of the chronic inflammation in the gut of IBD patients. This novel therapy is a dendritic cell DC that is engineered to de novo synthesize high concentrations of both the active vitamin D metabolite1,25OH2D and retinoid acid RA. We hypothesize that such engineered DC can home to and interact with T cells in the peripheral lymphoid tissues where the DC-derived and de novo synthesized focally high concentrations of 1,25OH2D and RA can promote the induction of regulatory and gut-homing molecules respectively in the same T cell that subsequently differentiates into a gut-homing Treg cell. We will test this hypothesis using an IBD animal model, i.e. experimental colitis.

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Technical Report,01 Aug 2016,31 Jul 2017



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Approved For Public Release;

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