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

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 transcr...

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Published inNature immunology Vol. 17; no. 7; pp. 878 - 887
Main Authors Dwyer, Daniel F, Barrett, Nora A, Austen, K Frank
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.07.2016
Subjects
Analysis
Animals
B cells
Basophils - physiology
Blood Cells - physiology
Cell Separation
Cells, Cultured
Cellular signal transduction
Connective Tissue Cells - physiology
Flow Cytometry
Gene expression
Gene Expression Profiling
Genetic aspects
Health aspects
Immune response
Immune system
Immunoglobulin E
Immunoglobulin E - metabolism
Immunoglobulins
Male
Mast cells
Mast Cells - physiology
Mice
Mice, Inbred C57BL
Observations
Physiological aspects
Properties
Spleen - cytology
Tissue Array Analysis
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Summary: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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Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Computer Science Department, Stanford University, Stanford, California, USA.
Division of Immunology, Department of Microbiology & Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Department of Life Sciences, Ben-Gurion University of the Negev, Be’er Sheva, Israel.
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Microbiology & Immunology, University of California San Francisco, San Francisco, California, USA.
These authors jointly supervised this work
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA.
Daniel F Dwyer1, Nora A Barrett1, K Frank Austen1, Edy Y Kim1, Michael B Brenner1, Laura Shaw3, Bingfei Yu3, Ananda Goldrath3, Sara Mostafavi4, Aviv Regev5, Andrew Rhoades6, Devapregasan Moodley6, Hideyuki Yoshida6, Diane Mathis6, Christophe Benoist6, Tsukasa Nabekura7, Viola Lam7, Lewis L Lanier7, Brian Brown8, Miriam Merad8, Viviana Cremasco9, Shannon Turley9, Paul Monach10, Michael L Dustin11, Yuesheng Li12, Susan A Shinton12, Richard R Hardy12, Tal Shay13, Yilin Qi14, Katelyn Sylvia14, Joonsoo Kang14, Keke Fairfax15, Gwendalyn J Randolph15, Michelle L Robinette15, Anja Fuchs16 & Marco Colonna15
The complete list of authors is as follows
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, Massachusetts, USA.
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA and Department of Cancer Immunology, Genentech, San Francisco, California, USA.
Division of Biological Sciences, University of California San Diego, La Jolla, California, USA.
Department of Medicine, Boston University, Boston, Massachusetts, USA.
Icahn Medical Institute, Mount Sinai Hospital, New York, New York, USA.
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
ISSN:1529-2908
1529-2916
1529-2916
DOI:10.1038/ni.3445