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Expression profiling of constitutive mast cells reveals a unique identity within the immune system

Nature Immunology volume 17, pages 878887 (2016) | Download Citation

Abstract

Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity receptor for immunoglobulin E (IgE) and have been linked to host defense and diverse immune-system-mediated diseases. To better characterize the function of these cells, we assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. We found that mast cells were transcriptionally distinct, clustering independently from all other profiled cells, and that mast cells demonstrated considerably greater heterogeneity across tissues than previously appreciated. We observed minimal homology between mast cells and basophils, which shared more overlap with other circulating granulocytes than with mast cells. The derivation of mast-cell and basophil transcriptional signatures underscores their differential capacities to detect environmental signals and influence the inflammatory milieu.

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Acknowledgements

We thank the other members of the ImmGen Consortium, especially C. Benoist and T. Shay, for discussions; the core ImmGen team, especially A. Rhodes and K. Rothamel, for technical assistance; and A. Chicoine for assistance with the isolation of cells. Supported by the US National Institutes of Health (R24AI072073 to the ImmGen Consortium; R01 HL120952 and U19AI095219 to N.A.B.; AI095219 to N.A.B.; and T32 AI007306 to D.F.D.) and the Steven and Judy Kaye Young Innovators Award (N.A.B.).

Author information

Author notes

    • Nora A Barrett
    •  & K Frank Austen

    These authors jointly supervised this work.

Affiliations

  1. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Daniel F Dwyer
    • , Nora A Barrett
    • , K Frank Austen
    • , Edy Y Kim
    •  & Michael B Brenner
  2. Harvard Medical School, Boston, Massachusetts, USA.

    • Daniel F Dwyer
    • , Nora A Barrett
    • , K Frank Austen
    • , Edy Y Kim
    •  & Michael B Brenner
  3. Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.

    • Laura Shaw
    • , Bingfei Yu
    •  & Ananda Goldrath
  4. Computer Science Department, Stanford University, Stanford, California, USA.

    • Sara Mostafavi
  5. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Aviv Regev
  6. Division of Immunology, Department of Microbiology & Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

    • Andrew Rhoades
    • , Devapregasan Moodley
    • , Hideyuki Yoshida
    • , Diane Mathis
    •  & Christophe Benoist
  7. Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California, USA.

    • Tsukasa Nabekura
    • , Viola Lam
    •  & Lewis L Lanier
  8. Icahn Medical Institute, Mount Sinai Hospital, New York, New York, USA.

    • Brian Brown
    •  & Miriam Merad
  9. Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA and Department of Cancer Immunology, Genentech, San Francisco, California, USA.

    • Viviana Cremasco
    •  & Shannon Turley
  10. Department of Medicine, Boston University, Boston, Massachusetts, USA.

    • Paul Monach
  11. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.

    • Michael L Dustin
  12. Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

    • Yuesheng Li
    • , Susan A Shinton
    •  & Richard R Hardy
  13. Department of Life Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel.

    • Tal Shay
  14. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

    • Yilin Qi
    • , Katelyn Sylvia
    •  & Joonsoo Kang
  15. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Keke Fairfax
    • , Gwendalyn J Randolph
    • , Michelle L Robinette
    •  & Marco Colonna
  16. Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Anja Fuchs

Consortia

  1. The Immunological Genome Project Consortium

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  1. Search for Daniel F Dwyer in:

  2. Search for Nora A Barrett in:

  3. Search for K Frank Austen in:

Contributions

D.F.D. wrote the manuscript, conceived of and conducted experiments, and analyzed the data; N.A.B. and K.F.A. wrote the manuscript and supervised the experimental design; and The ImmGen Project Consortium contributed to data collection and assisted in experimental design.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Nora A Barrett or K Frank Austen.

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DOI

https://doi.org/10.1038/ni.3445

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