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.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd2020-2607 |
| Date | 01 January 2023 |
| Creators | Long, Rodney |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations, 2020- |
Page generated in 0.0027 seconds