Gene expression profiling of WT and STAT3-/- Tc17 CD8+ T cells

CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (Tc17) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the cytotoxic transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.

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Ciucci T, Vacchio MS, Bosselut R