Abstract
Type I interferons (IFN) are unique cytokines transcribed from intronless genes. They have been extensively studied because of their anti-viral functions. The anti-viral effects of type I IFN are mediated in part by natural killer (NK) cells. However, the exact contribution of type I IFN on NK cell development, maturation and activation has been somewhat difficult to assess. In this study, we used a variety of approaches to define the consequences of the lack of type I interferon receptor (IFNAR) signaling on NK cells. Using IFNAR deficient mice, we found that type I IFN affect NK cell development at the pre-pro NK stage. We also found that systemic absence of IFNAR signaling impacts NK cell maturation with a significant increase in the CD27+CD11b+ double positive (DP) compartment in all organs. However, there is tissue specificity, and only in liver and bone marrow is the maturation defect strictly dependent on cell intrinsic IFNAR signaling. Finally, using adoptive transfer and mixed bone marrow approaches, we also show that cell intrinsic IFNAR signaling is not required for NK cell IFN-γ production in the context of MCMV infection. Taken together, our studies provide novel insights on how type I IFN receptor signaling regulates NK cell development and functions.
Highlights
Innate lymphoid cells comprise a large number of subsets, including natural killer (NK) cells [1]
We first compared the NK cell cellularity in IFNAR2/2 and littermate controls and found there were no significant differences in number or frequency in all tissues tested (Figure 1)
We investigated whether type I interferon receptor signaling had a significant role in the development of bone marrow derived NK cell populations
Summary
Innate lymphoid cells comprise a large number of subsets, including natural killer (NK) cells [1]. The effects of type I IFN signaling on NK cell development have been difficult to assess due to the pleiotropic nature of these cytokines [12]. In this study, using a variety of approaches, we defined the type I interferon receptor (IFNAR) signaling contribution to NK cell development and function. We found that IFNAR2/2 mice have a significant increase in the CD27+CD11b+ NK cell compartment in all organs While this maturation effect is direct in the liver and bone marrow, it is indirect in the spleen and blood, indicating tissue specificity. Using adoptive transfer and mixed bone marrow approaches, we show that NK cell IFN-c production is not affected by lack of type I IFN signaling in the context of MCMV infection
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