Impaired AHR Signaling Contributes To Intestinal ILC3/ILC1 Conversion In The Inflamed Terminal Ileum Of Crohn’s Disease Patients

Abstract Introduction Crohn’s disease (CD) is one form of inflammatory bowel disease (IBD). Traditionally, adaptive immunity has been presumed to play a major role in the pathogenesis of CD. Recently, increasing evidence indicates that innate immunity also plays an essential role in this process. The phenotype and function of newly discovered innate lymphoid cells (ILCs) are crucial for the maintenance of intestinal homeostasis. Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which is important for the regulation of ILC biology in the mouse gut. We wanted to explore the potential involvement of AHR in the regulation of intestinal ILC of CD patients. Hypothesis AHR signaling pathway is critical for the regulation of the phenotype and function of human intestinal ILC in the terminal ileum of CD patients. Methods Surgical terminal ileum samples were collected from CD patients. Histology, Real-time PCR analysis, flow cytometric analysis and immunohistochemistry staining were performed. Results The expression of AHR was correlated with CD117 expression on human intestinal ILC subsets. The IFN-γ-producing-ILC1s accumulated in the inflamed terminal ileum of CD patients at the expense of protective IL-22-producing NKp44+ILC3s. Also, the expression of both AHR and CD117 were downregulated in the ILCs from the inflamed tissue. Additionally, there was a disparity between AHR protein and mRNA expression in the inflamed gut of CD patients which suggested the involvement of a posttranscriptional mechanism. Conclusions The AHR signaling was impaired in the inflamed gut of CD patients. This transcriptional modification contributed to the ILC3/ILC1 conversion and promoted the process of intestinal inflammation.