The pathogenicity of irritable bowel disease (IBD) is attributed to chronic gastrointestinal inflammation with acute flare-ups. While the regulation of pathogenic inflammation is debated, evidence suggests key contributions from Type-1 and Type-17 helper T-cells and their innate counterparts, class 1 and 3 innate lymphoid cells. The differentiation of these adaptive and innate effector cells is primarily directed by so-called 'master regulator' transcription factors: T-box Expressed in T-cells (T-bet) drives development of Type-1 helper T cells and class I innate lymphoid cells, while Retinoic acid-related Orphan Receptor γ-t (RORγt) promotes development of Type-17 helper T cells and class 3 innate lymphoid cells. The relationship between these transcription factors is largely antagonistic, leading to either prominent Type-1 or Type-17 inflammation, but maladaptive plasticity and concurrent responses have been reported in IBD patients. Deciphering roles for T-bet and ROR?t in experimental settings is difficult as the absence of one often leads to the overexpression of the other. We thus created mice deficient for both T-bet and RORγt to study acute colitis in the absence of major drivers of both Type-1 and Type-17 inflammation. A widely used inducer of experimental colitis, dextran sodium sulfate, was given to mice in their drinking water to determine acute disease progression during a 7-day period using traditional metrics and kinetic analysis of multiple metrics using a metabolic cage system. Our results indicate, surprisingly, that the dual absence of T-bet and RORγt does not appreciably affect the susceptibility or severity of acute DSS colitis. These studies may provide a basis to uncover new biomarkers, disease mechanisms, and therapeutic targets in the setting of IBD.
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Master of Science (M.S.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Masters Thesis (Campus-only Access)
Long, Rodney, "Analysis of Acute Colitis in Mice Deficient for Master Regulators of Both Type-1 and Type-17 Inflammation Using Traditional Readouts and Metabolic and Behavioral Data" (2023). Electronic Theses and Dissertations, 2020-. 1608.
Restricted to the UCF community until May 2028; it will then be open access.