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Date of Award
Doctor of Philosophy (PhD)
Type 3 innate lymphoid cells (ILC3) provide an innate source of IL-22 and IL-17 that has been proposed to be essential for intestinal defense against pathogenic bacteria. ILC3 can be divided into two major subsets: NKp46+ ILC3 and LTi-like NKp46– ILC3. Since both subsets depend on RORt and AHR for development, we utilized these two transcription factors to generate mutant mice to study the roles of ILC3 in intestinal immunity (Chapter 2). To date, it is unclear whether NKp46+ and LTi-like ILC3 subsets are redundant or have specialized functions. We found that NKp46+ ILC3 subsets play a pathogenic role in the anti-CD40 colitis, an innate colitis model, by eliciting accumulation of inflammatory monocytes in intestinal tissues. ILC3 function in this model is driven by their ability to secrete GM-CSF, which directs inflammatory monocyte activation and produces a positive feedback loop by eliciting further IL-23 and IL-1b production by monocytes, which sustains activation of ILC3 (Chapter 3). We also used other models to study the role of ILC3 in intestinal immunity, such as Citrobacter rodentium infection, DSS-induced colitis, and the AOM/DSS colon cancer model (Chapter 4). We found that ILC3 are partially protective during C. rodentium infection, but are unimportant to the development or pathogenesis of DSS-induced colitis or AOM/DSS-induced colon tumorigenesis. In conclusion, ILC3 have variegated functions in intestinal immunity and appear to be important mediators of inflammation and barrier integrity at mucosal surfaces.
Chair and Committee
Thaddeus Stappenbeck, Paul Allen, Rodney Newberry, Jeffrey Gordon
Song, Christina, "Identifying the Functions of ILC3 in Intestinal Immunity" (2015). Arts & Sciences Electronic Theses and Dissertations. 682.
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