title: Aryl hydrocarbon receptor signaling involves in the human intestinal ILC3/ILC1 conversion in the inflamed terminal ileum of Crohn's disease patients.
abstract: Innate lymphoid cells (ILCs) are emerging as important components of our immune system that have critical effector and regulatory functions in both innate and adaptive immune responses. They are enriched at mucosal surfaces, such as lung and intestine. Our previous work has shown that Lineage-CRTH2-CD45+NKp44-CD117-CD127+ILC1s accumulated in the inflamed terminal ileum of patients with Crohn's disease (CD) at the expense of NKp44+ILC3s. This phenotype conversion impairs the intestinal barrier integrity and contributes to the dysregulated immune responses of CD patients. Our next step was to search for pathways to modulate this phenotype switch. The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor. Initial studies of AHR concentrated on its role in the detoxification of xenobiotics. However, recent research has focused on the immune system. Especially, AHR pathway is proven to be essential for the maintenance of intestinal ILC3s in mouse models. We examined whether AHR pathway participated in the human intestinal ILC phenotype change in the inflamed terminal ileum of CD patients. As anticipated, NKp44+ILC3s, NKp44-ILC3s and ILC1s had differential AHR expression. This AHR signaling mediated CD117 expression on the surface of ILC3s. The conversion from ILC3 to ILC1 was accompanied by the downregulation of AHR expression. We further observed that there was a disparity between AHR protein expression and mRNA expression in the inflamed terminal ileum tissues of CD patients compared to unaffected areas. These findings suggest that AHR pathway is also important for human intestinal ILC phenotype regulation and impaired AHR signaling in the inflamed gut of CD patients possibly contributes to the ILC3/ILC1 conversion.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida P.O. Box 100214, Gainesville, FL, 32610 USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida P.O. Box 100214, Gainesville, FL, 32610 USA.
authors.forename: Andria
authors.initials: A
authors.lastname: Doty
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Florida P.O. Box 100214, Gainesville, FL, 32610 USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Glover
keywords: AHR; CD; ILC; terminal ileum