Type I interferon supports γδ T-cell homeostasis and immunity through direct and indirect receptor signaling in mice.

Interleukin (IL)-17-producing gamma delta (γδ) T (γδT17) cells are an essential part of innate type 3 immunity against numerous pathogens. At the same time, a large body of evidence from mouse models and human clinical studies suggests that γδT17 cells contribute to the pathogenesis of many inflammatory diseases as well as cancer. It is therefore relevant to elucidate their immunobiology in detail and identify molecules and pathways that can regulate their function. Herein, we investigated the importance of the type I interferon (IFN) signaling system in γδT17 homeostasis and activation. We found that the IFN alpha receptor 1 (IFNAR1) was critical to maintain their normal homeostasis and to promote their activation during cutaneous inflammation. However, this did not require γδT17-intrinsic expression of IFNAR1. In contrast, expression of IFNAR1 by γδT17 cells was required in order to suppress IL-17 production during viral infection. Our data delineate direct from indirect IFNAR1 signaling and reveal an important immunoregulatory role for both tonic and inducible type I IFN in γδT17 cells.