Type I interferon regulation of group I ILC subsets during both homeostasis and cytomegalovirus infection.

Type 1 innate lymphoid cells (ILC1s) and conventional natural killer cells belong to the group 1 ILCs (gILC1), characterized largely by T-bet expression and interferon γ secretion. While much has been done to define factors that regulate the development, differentiation, and effector functions of both cell types, little is known about what controls gILC1 homeostasis. Here, mixed bone marrow chimeras were used to define the role of type I interferon receptor (IFNAR) signaling in regulating gILC1 in the spleen and liver at homeostasis and during murine cytomegalovirus infection. We show that basal IFNAR signaling induces cell and tissue-specific phenotypic changes in gILC1, inhibiting bona-fide ILC1 markers (CD49a, CD200R, CXCR6) and regulating expression of perforin and granzymes B and C. Finally, while IFNAR signaling enhances cytokine responsiveness in vitro in both gILC1 subsets, it has a dichotomous effect on interferon γ production during murine cytomegalovirus infection, stimulating it in conventional natural killer cells and inhibiting it in ILC1.