title: Proliferation conditions promote intrinsic changes in NK cells for an IL-10 response.
abstract: Constitutively found at high frequencies, the role for NK cell proliferation remains unclear. In this study, a shift in NK cell function from predominantly producing IFN-γ, a cytokine with proinflammatory and antimicrobial functions, to producing the immunoregulatory cytokine IL-10 was defined during extended murine CMV infection. The response occurred at times subsequent to IL-12 production, but the NK cells elicited acquired responsiveness to IL-12 and IL-21 for IL-10 production. Because neither IL-12 nor IL-21 was required in vivo, however, additional pathways appeared to be available to promote NK cell IL-10 expression. In vitro studies with IL-2 to support proliferation and in vivo adoptive transfers into murine CMV-infected mice demonstrated that NK cell proliferation and further division enhanced the change. In contrast to the sustained open profile of the IFN-γ gene, NK cells responding to infection acquired histone modifications in the IL-10 gene indicative of changing from a closed to an open state. The IL-10 response to IL-12 was proliferation dependent ex vivo if the NK cells had not yet expanded in vivo but independent if they had. Thus, a novel role for proliferation in supporting changing innate cell function is reported.
authors.affiliation: Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912;
authors.forename: Margarite L
authors.initials: ML
authors.lastname: Tarrio
authors.affiliation: Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912;
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912;
authors.forename: Maria F
authors.initials: MF
authors.lastname: Fragoso
authors.affiliation: Biodata Mining and Discovery Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Sun
authors.affiliation: Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.affiliation: Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
authors.affiliation: Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912; Christine_Biron@brown.edu.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Biron
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: C556062:IL10 protein, mouse; D007378:Interleukins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D000098546:Interleukin-21