title: Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.
abstract: 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 confirmed 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-deficient DCs ex vivo, intestinal organoids showed reduced SRY (sex determining region Y)-box 9 and increased Mucin 2 expression, which correlates with reduced Paneth cells and increased goblet cell differentiation, 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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.|Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.|Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, S-171 77, Sweden.
authors.forename: Song Hui
authors.initials: SH
authors.lastname: Chng
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
authors.forename: Parag
authors.initials: P
authors.lastname: Kundu
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Carmen
authors.initials: C
authors.lastname: Dominguez-Brauer
authors.affiliation: National Cancer Centre of Singapore, Singapore 169610, Singapore.
authors.forename: Wei Ling
authors.initials: WL
authors.lastname: Teo
authors.affiliation: Saitama Cancer Center Research Institute for Clinical Oncology, 818 Komuro, Inanmachi, Kitaadachi-gun, Saitama, 361-0806 Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Kawajiri
authors.affiliation: Tokyo Medical and Dental University, Medical Research Institute, 2-3-10 Kanda-Surugadai Chiyodaku, Tokyo 101-0062 Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario M5G 2C1, Canada.
authors.forename: Tak Wah
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.|Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, S-171 77, Sweden.|Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232.
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000737:chemistry / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D039521:CD11c Antigen / Q000032:analysis*; D002454:Cell Differentiation; D018920:Coculture Techniques; D003092:Colitis / Q000473:pathology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000254:growth & development* / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009940:Organoids; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D039521:CD11c Antigen; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse