Type I interferon is critical for the homeostasis and functional maturation of type 3 γδ T cells

Type I IFN (IFN-I) is highly expressed during viral infection and many autoimmune pathologies such as SLE and psoriasis. In addition, IFN-I is important to maintain the homeostasis of a number of different immune populations. Our aim was to identify whether IFN-I regulates type 3 γδ T (γδT3) cells. We found that IFNαβ inhibits the activation of γδT3 cells following treatment with cytokines such as IL-23 and IL-7 and abrogates their ability to produce IL-17 during viral infection. Despite this inhibitory role, γδT3 cells that are deficient in type I IFNreceptor (IFNAR) signaling display anergic behavior. Such γδT3 anergy is characterized by failure to induce skin inflammation and unresponsiveness to cytokine stimuli. Moreover, IFNAR deficient mice display deregulated γδT3homeostasis due to a neonatal maturation defect. In conclusion, our data show that tonic type I IFN signaling during neonatal and adult life is required for the full maturation and pro-inflammatory function of γδT3 cells, however acute type I IFN production during viral infection acts as a γδT3 inhibitor.