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

Restorick, Siobhan Margaret (2014). Overlap of cytokine and transcription factor expression in T helper cell subsets. University of Birmingham. Ph.D.

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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:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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