An endogenous aryl hydrocarbon receptor (AhR) ligand, ITE induces regulatory T cells (Tregs) and ameliorates experimental colitis (IRC4P.490)

Abstract

Abstract Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that affects millions of people with high morbidity and health-care cost. Recent studies have shown that activation of the aryl hydrocarbon receptor (AhR) with the nontoxic ligand 2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces regulatory T cells (Tregs) and suppresses autoimmune diseases. However, the effects of ITE on experimental colitis have not been investigated. We hypothesized that ITE induces in-vitro and in-vivo Tregs through activation of AhR and suppresses experimental colitis. Our data showed that ITE increases the frequency of Tregs in spleen, MLN and LPL as compared to vehicle. This induction of Tregs was reversed by AhR antagonist treatment in-vitro. Next, in-vivo colitis pathogenesis including a decrease in body weight was significantly reversed and systemic inflammatory cytokines were reduced in mice that received ITE treatments as compared to vehicle. ITE treatment also increased CD11c+, decreased activated T and CD11b+ cells from the spleen, MLN and LP as compared to vehicle alone. These findings clearly suggest that ITE diminishes colitis pathology through induction of Tregs, reduces inflammatory cytokines, decreases the inflammation score, and induces dendritic cells resulting in amelioration of colitis. Thus, our work demonstrates that the nontoxic endogenous AhR ligand, ITE, may serve as unique treatment modality against IBD.