Song Hui Chng, Parag Kundu, Carmen Dominguez-Brauer, Wei Ling Teo, Kaname Kawajiri, Yoshiaki Fujii-Kuriyama, Tak Wah Mak & Sven Pettersson

Scientific Reports 2016 Apr 12; 6:23820

PMID: 27068235

Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has con rmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs)
is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Moreover, when co-cultured with AhR-de cient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining regionY)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell di erentiation, similar to the data obtained in vivo. Further, characterization of intestinal APC subsets, devoid of AhR, revealed an expression pattern associated with aberrant intrinsic Wnt pathway regulation. At a functional level, the loss of AhR in APCs resulted in a dysfunctional epithelial barrier, associated with a more aggressive chemically induced colitis compared to wild type animals. Our results are consistent with a model whereby the AhR signalling pathway may participate in the regulation of innate immunity through intestinal epithelium development and mucosal immunity.