Accession Number : AD1046756


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


Descriptive Note : Technical Report,01 Aug 2016,31 Jul 2017


Corporate Author : Loma Linda University Loma Linda United States


Personal Author(s) : Tang,Xiaolei ; Xu,Yi ; Qin,Xuezhong


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1046756.pdf


Report Date : 01 Aug 2017


Pagination or Media Count : 26


Abstract : Inflammatory bowel disease (IBD) is a group of diseases that are conditions of chronic inflammation in the gastrointestinal tract(the 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 metabolite[1,25(OH)2D] 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 1,25(OH)2D 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.


Descriptors :   INTESTINAL DISEASES , inflammation , GASTROINTESTINAL DISEASES , therapeutics


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE