Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS Biol. 2014 Jan;12(1):e1001762. doi: 10.1371/journal.pbio.1001762. Epub 2014 Jan 14.

A20-deficient mast cells exacerbate inflammatory responses in vivo.

Author information

1
Molecular Immunology and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
2
Laboratory of Immunoregulation, Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium ; Department for Molecular Biomedical Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium.
3
Department of Surgery, Ludwig Maximilians Universität, Munich, Germany.
4
Institute for Immunology, Technische Universität Dresden, Dresden, Germany.
5
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
6
Department for Molecular Biomedical Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium ; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
7
II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
8
Laboratory of Immunoregulation, Department of Pulmonary Medicine, University Hospital Ghent, Ghent, Belgium ; Department for Molecular Biomedical Research, Vlaams Instituut voor Biotechnologie, Ghent, Belgium ; Department of Pulmonary Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

Abstract

Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-κB negative feedback regulator A20. While A20 deficiency did not affect mast cell degranulation, it resulted in amplified pro-inflammatory responses downstream of IgE/FcεRI, TLRs, IL-1R, and IL-33R. As a consequence house dust mite- and IL-33-driven lung inflammation, late phase cutaneous anaphylaxis, and collagen-induced arthritis were aggravated, in contrast to experimental autoimmune encephalomyelitis and immediate anaphylaxis. Our results provide in vivo evidence that hyperactive mast cells can exacerbate inflammatory disorders and define diseases that might benefit from therapeutic intervention with mast cell function.

PMID:
24453940
PMCID:
PMC3891641
DOI:
10.1371/journal.pbio.1001762
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors have declared that no competing interests exist.

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center