Date of Award
8-19-2024
Document Type
Open Access Dissertation
Department
Biomedical Science
First Advisor
Philip Busbee
Abstract
Colitis is an inflammatory bowel disease characterized by dysregulation of the immune system that results in chronic inflammation and dysbiosis. Previously we showed that a naturally sourced aryl hydrocarbon receptor (AhR) ligand, indole-3-carbinol (I3C), was effective in the reduction of colitis-associated disease severity through innate lymphoid type 3 cells (ILC3s) in an interleukin-22 (IL-22) dependent manner. In one of our studies, we used single cell RNA sequencing (scRNAseq) analysis of colonic lamina propria cells from colitis models treated with I3C. Our results indicated that there were changes in the expressions of genes integral to IL-22 signaling when I3C was used a treatment. We also generated conditional knockout mice that had AhR deficiency in Rorc-expressing cells (AhRΔRorc) and found that AhRΔRorc mice lost the expected efficacy effects of I3C treatment which resulted in the loss of IL-22 production by ILC3s.
Additionally, colitis disrupts the microbial homeostasis of the gut and results in microbial dysbiosis. This disruption is a dominant influence in colitis disease development, severity, and how the host responds to treatment. We performed gut bacteria profiling of the fecal samples from experimental mice, which showed that there were sex-linked differences in the microbiome with colitis and I3C treatment, which differed depending on whether or not AhR was present in Rorc-expressing cells. Results also showed that the abundance of Bacteroides, which was increased during colitis-induced states, was significantly impacted by AhR. Collectively, the data from these studies show that AhR expression in ILC3s plays an important role in protecting against colitis severity via regulation of IL-22 production. It also highlights the AhR-ILC3-IL-22 pathway and how it regulates colitis-associated microbial dysbiosis, specifically in regulating the abundance of certain bacteria within the gut microbiome.
Rights
© 2024, Chandani Mitchell
Recommended Citation
Mitchell, C.(2024). The Crucial Role of the Ahr-ilc3-il22 Pathway in I3c-mediated Protection Against Colitis and Associated Microbial Dysbiosis. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7802