title: Role of type I interferon receptor signaling on NK cell development and functions.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Jean
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: S M Shahjahan
authors.initials: SM
authors.lastname: Miah
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Wilson
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Erick
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Cindy
authors.initials: C
authors.lastname: Banh
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brossay
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology / Q000472:pathogenicity; D009928:Organ Specificity; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C508032:Ifnar1 protein, mouse; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma