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Overlap of cytokine and transcription factor expression in T helper cell subsets

Restorick, Siobhan Margaret (2014)
Ph.D. thesis, University of Birmingham.

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Abstract

Until recently, CD4\(^+\)THelper (T\(_H\)) cells were thought to be permanently committed to a single lineage (e.g. T\(_H\)1, T\(_H\)17, T\(_H\)2 etc.). However there is now increasing evidence that T\(_H\) cells are plastic in nature and can gain phenotypic feature of other TH cells. Within this study I have investigated the overlap and plasticity of T\(_H\)1 cells and their presence in health and in the inflammatory setting of multiple sclerosis.

Although CCR6 is considered a T\(_H\)17 marker there are other T\(_H\)cell subsets that express CCR6. I have identified a novel subset of T\(_H\)1 cells that express functional CCR6. CCR6\(^+\)T\(_H\)1 cells transcriptionally express 'T\(_H\)17'-related genes (e.g. RORC, IL-23R and IL4I1) but are distinct from IFN\(\gamma\)\(^+\)IL-17\(^+\) cells that also express CCR6, RORC and T-bet. Additionally I have identified candidate miRNAs that may play a role in controlling phenotypic features of these cells. T\(_H\)17 cells have been implicated in the pathogenesis of multiple sclerosis and enter the cerebrospinal fluid through CCR6-dependent migration. CCR6\(^+\)IFN\(\gamma\)\(^+\) cells were increased within the cerebrospinal fluid of patients with multiple sclerosis, suggesting a possible role in disease pathogenesis.

Type of Work:Ph.D. thesis.
Supervisor(s):Curnow, SJ
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QR180 Immunology
R Medicine (General)
Institution:University of Birmingham
ID Code:4808
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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