Identification of effector gamma delta T cell subset-specific regulators by signature cytokine-associated transcriptome analysis

Two key subsets of effector gamma delta T cells, producing either interleukin-17A (gamma delta 17) or interferon gamma (gamma delta IFN), are generated in the mouse thymus, but the molecular regulators of their peripheral functions remain poorly characterized. Here we established an Il17a-GFP:Ifng-YFP double reporter mouse strain to analyse the transcriptomes of pure gamma-delta 17 versus gamma delta IFN populations from peripheral lymph nodes in the steady-state. Genome-wide RNA-seq revealed a surprisingly high (49%) fraction of the >12,800 genes transcribed in gamma delta T cells to be differentially expressed between the two effector subsets. We identified and validated a panel of 20 new signature genes in gamma delta 17 versus gamma delta IFN cells, whose expression levels often increased between the thymus and peripheral organs, suggesting a progressive effector differentiation process.