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The miR-126–VEGFR2 axis controls the innate response to pathogen-associated nucleic acids

Nature Immunology volume 15, pages 5462 (2014) | Download Citation

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.

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Acknowledgements

We thank C.J. Kuo (Stanford University) for Mir126−/− mice; P. Sathe, R. Sachidanandam, L. Naldini and B. Gentner for discussions; J. Ochando for reading the manuscript; and the Mount Sinai Mouse Genetics and Mouse Targeting facility, the Flow Cytometry Core and the Mount Sinai Genomics Core for technical assistance. Supported by the US National Institutes of Health (DP2DK083052 and 1R01AI104848 to B.D.B., and CA154947A, AI10008 and AI089987 to M.M.), the Beatriu de Pinós program (J.A.), and the Juvenile Diabetes Research Foundation (J.A.).

Author information

Affiliations

  1. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Judith Agudo
    • , Albert Ruzo
    • , Navpreet Tung
    • , Alessia Baccarini
    •  & Brian D Brown
  2. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Hélène Salmon
    • , Marylène Leboeuf
    • , Daigo Hashimoto
    • , Christian Becker
    •  & Miriam Merad
  3. Mount Sinai Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

    • Hélène Salmon
    • , Marylène Leboeuf
    • , Daigo Hashimoto
    • , Christian Becker
    • , Miriam Merad
    •  & Brian D Brown
  4. Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York, USA.

    • Lee-Ann Garrett-Sinha

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Contributions

J.A. designed and did research and analyzed data; A.R., N.T., H.S., M.L., D.H., C.B., L.-A.G.-S. and A.B. did research; M.M. designed the project and analyzed data; and B.D.B. designed and coordinated the project and analyzed data.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Brian D Brown.

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    Predicted targets of miR-126.

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DOI

https://doi.org/10.1038/ni.2767

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