Identification of a specific gene signature in human Th1/17 cells (BA13P.126)

T cells that co-express the chemokine receptors CCR6 and CXCR3 and produce IL-17, IFN-γ, GM-CSF and low IL-10, also known as Th1/17 cells, have been proposed to be highly pathogenic in several autoimmune disorders. To better characterize these cells and examine their relationship with Th1 and Th17 cells, we compared the whole transcriptome of the aforementioned T cell subsets by RNAseq directly ex vivo. Using this approach, we identified groups of genes shared either with Th1 or Th17 cells. The Th1 signature included genes such as TBX21, IL12RB2, GZMK, PRF1 and CCL5, whereas the Th17 signature contained well-established Th17-associated genes (i.e. RORC and KLRB1) as well as those not previously associated with Th17 cells (i.e. CTSH and PTPN13). Interestingly, we also found genes specifically expressed by Th1/17 cells, among which are IL4i1, LTK and ABCB1. The latter, also known as MDR1, encodes for a transmembrane transporter playing a major role in the efflux of drugs and endogenous metabolites across the cell membrane. We confirmed its unique expression on Th1/17 cells using a rhodamine efflux assay. Moreover, MDR1+ Th1/17 cells displayed a highly pro-inflammatory cytokine profile. Our data reinforce the notion that Th1/17 cells are a heterogeneous population of cells combining Th1 and Th17 phenotypic and functional characteristics but also that these cells have unique properties that could be targeted as new strategies to combat autoimmune diseases.