IFN‐γ and IL‐12 synergize to convert in vivo generated Th17 into Th1/Th17 cells

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Abstract
Th1 and Th17 cells are distinct lineages of effector/memory cells, imprinted for re‐expression of IFN‐γ and IL‐17, by upregulated expression of T‐bet and retinoic acid‐related orphan receptor γt (RORγt), respectively. Apparently, Th1 and Th17 cells share tasks in the control of inflammatory immune responses. Th cells coexpressing IFN‐γ and IL‐17 have been observed in vivo, but it remained elusive, how these cells had been generated and whether they represent a distinct lineage of Th differentiation. It has been shown that ex vivo isolated Th1 and Th17 cells are not interconvertable by TGF‐β/IL‐6 and IL‐12, respectively. Here, we show that ex vivo isolated Th17 cells can be converted into Th1/Th17 cells by combined IFN‐γ and IL‐12 signaling. IFN‐γ is required to upregulate expression of the IL‐12Rβ2 chain, and IL‐12 for Th1 polarization. These Th1/Th17 cells stably coexpress RORγt and T‐bet at the single‐cell level. Our results suggest a molecular pathway for the generation of Th1/Th17 cells in vivo, which combine the pro‐inflammatory potential of Th1 and Th17 cells.

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