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

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