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.