title: The miR-126-VEGFR2 axis controls the innate response to pathogen-associated nucleic acids.
abstract: miR-126 is a microRNA expressed predominately by endothelial cells and controls angiogenesis. We found miR-126 was required for the innate response to pathogen-associated nucleic acids and that miR-126-deficient mice had greater susceptibility to infection with pseudotyped HIV. Profiling of miRNA indicated that miR-126 had high and specific expression by plasmacytoid dendritic cells (pDCs). Moreover, miR-126 controlled the survival and function of pDCs and regulated the expression of genes encoding molecules involved in the innate response, including Tlr7, Tlr9 and Nfkb1, as well as Kdr, which encodes the growth factor receptor VEGFR2. Deletion of Kdr in DCs resulted in reduced production of type I interferon, which supports the proposal of a role for VEGFR2 in miR-126 regulation of pDCs. Our studies identify the miR-126-VEGFR2 axis as an important regulator of the innate response that operates through multiscale control of pDCs.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Agudo
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Ruzo
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Navpreet
authors.initials: N
authors.lastname: Tung
authors.affiliation: 1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Hélène
authors.initials: H
authors.lastname: Salmon
authors.affiliation: 1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Marylène
authors.initials: M
authors.lastname: Leboeuf
authors.affiliation: 1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Daigo
authors.initials: D
authors.lastname: Hashimoto
authors.affiliation: 1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.affiliation: Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Lee-Ann
authors.initials: LA
authors.lastname: Garrett-Sinha
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Baccarini
authors.affiliation: 1] Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.affiliation: 1] Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. [2] Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Brown
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D015151:Immunoblotting; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009696:Nucleic Acids / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D009696:Nucleic Acids; D009838:Oligodeoxyribonucleotides; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C073701:Nfkb1 protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2