Abstract
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.
Notes
If this is your thesis or dissertation, and want to learn how to access it or for more information about readership statistics, contact us at STARS@ucf.edu
Graduation Date
2023
Semester
Spring
Advisor
McKinstry, Karl
Degree
Master of Science (M.S.)
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Degree Program
Biotechnology
Identifier
CFE0009565; DP0027575
URL
https://purls.library.ucf.edu/go/DP0027575
Language
English
Release Date
May 2028
Length of Campus-only Access
5 years
Access Status
Masters Thesis (Campus-only Access)
STARS Citation
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, 2020-2023. 1608.
https://stars.library.ucf.edu/etd2020/1608
Restricted to the UCF community until May 2028; it will then be open access.