Date of Award
Summer 5-10-2024
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biomedical Sciences
First Advisor
Timothy L. Denning
Second Advisor
Andrew Gewirtz
Third Advisor
Leszek Ignatowicz
Abstract
Inflammatory bowel disease (IBD) continues to affect millions worldwide, with an increasing prevalence that highlights the urgent need for deeper understanding of its underlying immune mechanisms. The cytokine interactions, especially those mediated by cells from the TH1 and TH17 lymphocyte subsets, are crucial in orchestrating the immune landscape of IBD. TH1 cells are well known for producing TNF-α and IFNγ, which have been extensively studied for their roles in conjunction with each other within the context of IBD (Fish, 1999). TH17 cells secrete IL-22 and IL-17, with existing studies primarily focusing on IL-22’s interaction with IL-17 rather than its interplay with other cytokines such as IFNγ. Our study focuses on the co-stimulatory effects of IL-22 and IFNγ using organoids derived from mouse small intestines to model epithelial interactions. We found that IFNγ interferes with the capacity of IL-22 to up-regulate antimicrobial peptides, which is essential in mucosal defense. Additionally, higher concentrations of IL-22 enhance IFNγ's ability to stimulate TNF-α gene expression and CXCL10 protein production, indicating a dose-dependent relationship. This co-stimulation also led to an increased rate of cell death, influenced partly by TNF-α. These findings suggest that IL-22, typically seen as an anti-inflammatory agent, can assume a pro-inflammatory role when combined with IFNγ, complicating its effects on epithelial cells. This study highlights the need to consider specific cytokine interactions in developing more effective IBD treatments.
DOI
https://doi.org/10.57709/37114426
Recommended Citation
Johnson, Asia E., "Modulatory Effects of IFN-γ and IL-22 on Inflammatory Signaling and Cellular Responses in Intestinal Epithelial Cells." Dissertation, Georgia State University, 2024.
doi: https://doi.org/10.57709/37114426