3,3′-Diindolylmethane alleviates oxazolone-induced colitis through Th2/Th17 suppression and Treg induction

Abstract

The T cell is pivotal in orchestrating and promoting an immune response during ulcerative colitis (UC). The aryl hydrocarbon receptor (AhR) is involved in the regulation of T cell responses, and 3,3′-diindolylmethane (DIM) is a known ligand of AhR. The aim of this study was to examine the therapeutic effects of DIM in experimental colitis and to investigate the possible mechanisms underlying its effects on mucosal T cell responses. The therapeutic effects of DIM were studied in an oxazolone-induced colitis model. The pathologic markers of colitis were measured, moreover, T-helper cell (Th)- and regulatory T cell (Treg)-related transcription factor expression and associated colonic cytokine production were determined. The impact of DIM on T cell differentiation was further investigated in cultures of naive Th cells that were stimulated with anti-CD3/CD28 monoclonal antibodies (mAbs). The administration of DIM attenuated experimental colitis, as determined by pathological indices. DIM may affect signaling pathways downstream of AhR, leading to decreased Th2/Th17 cells and increased Tregs. Ultimately, this could result in the alleviation of experimental colitis. DIM has shown anti-UC activity in animal models via inhibition of Th2/Th17 cells and promotion of Tregs and may thus offer potential treatments for UC patients.