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)

Restricted to the UCF community until May 2028; it will then be open access.

Share

COinS