Opposing role of type-I IFN for cNK and ILC1 during homeostasis and infection 2491

Abstract Description Type-I innate lymphoid cells (ILC1) and conventional natural killer (cNK) cells belong to the group-I ILCs (gILC1), characterized largely by T-bet expression, IFNγ secretion, and cytotoxic activity. 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. This is however meaningful given the ability of those cells to readily activate within hours following an infection. 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 (MCMV) 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 granzyme B and C, in a cell-type specific manner. Importantly, while IFNAR signaling enhances cytokine responsiveness in vitro in both gILC1 subsets, it has a dichotomous effect on IFNγ production during MCMV infection, stimulating it in cNK and inhibiting it in ILC1. Collectively, our study suggests that while ILC1 and cNK share lots of common traits in regards of development, phenotype and effector functions, they can respond in opposite manner to type-I IFNs, which could be a mechanism used by the immune system to diversify the immune response to an infection. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)