Work

AhR-dependent induction of β-defensin 1 in colonic epithelial cells regulates cross-talk between gut microbiota and immune response leading to attenuation of colitis 3174

Year: 2025

Type: article

Abstract: Description The aryl hydrocarbon receptor (AhR) acts as a critical signaling hub that connects immune cells, food and environmental cues, and microbiota to regulate intestinal homeostasis. In the current study, we investigated the role of AhR in the regulation of an antimicrobial peptide, b-defensin1 (BD-1) to control colitis. Human patients with ulcerative colitis (UC) and Crohn’s disease (CD), and mice with experimental colitis expressed significant decrease in the expression of BD-1 in colonic epithelial cells (CECs). AhR ligands induced the expression of BD-1 in CECs through the activation of two dioxin responsive elements (DREs) expressed on its promoter. AhR ligands attenuated colitis in wild-type mice while inducing BD-1. However, AhR ligands failed to induce BD-1 and protect mice from colitis when there was an intestinal epithelial cell (IEC)-specific deletion of AhR. Blocking BD1 in vivo using Abs prevented the ability of AhR ligands to attenuate colitis, restore dysbiosis and attenuate colonic inflammation. The current study identifies a novel pathway involving AhR-dependent induction of BD-1 by IECs, to play a critical role in the regulation of intestinal homeostasis. Funding Sources This work was supported in part by NIH grants R01ES030144, P01AT003961, P20GM103641, and R01AI123947, R01AI160896 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1003