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Cell Rep. 2014 Jan 30;6(2):366-76. doi: 10.1016/j.celrep.2013.12.029. Epub 2014 Jan 9.

Critical role for mast cell Stat5 activity in skin inflammation.

Author information

1
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
2
Division of Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, MD 21224, USA.
3
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
4
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
5
Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama 230-0045, Japan.
6
Division of Dermatology, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA.
7
Division of Medical Biochemistry, Department of Biomolecular Sciences and Department of Laboratory Medicine, Saga Medical School, Saga 849-85-01, Japan.
8
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
9
Institute for Immunology, University of Technology Dresden, Medical Faculty Carl-Gustav Carus, 01307 Dresden, Germany.
10
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA; Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama 230-0045, Japan. Electronic address: toshi@lji.org.

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Here, we show that phospholipase C-β3 (PLC-β3)-deficient mice spontaneously develop AD-like skin lesions and more severe allergen-induced dermatitis than wild-type mice. Mast cells were required for both AD models and remarkably increased in the skin of Plcb3(-/-) mice because of the increased Stat5 and reduced SHP-1 activities. Mast cell-specific deletion of Stat5 gene ameliorated allergen-induced dermatitis, whereas that of Shp1 gene encoding Stat5-inactivating SHP-1 exacerbated it. PLC-β3 regulates the expression of periostin in fibroblasts and TSLP in keratinocytes, two proteins critically involved in AD pathogenesis. Furthermore, polymorphisms in PLCB3, SHP1, STAT5A, and STAT5B genes were associated with human AD. Mast cell expression of PLC-β3 was inversely correlated with that of phospho-STAT5, and increased mast cells with high levels of phospho-STAT5 were found in lesional skin of some AD patients. Therefore, STAT5 regulatory mechanisms in mast cells are important for AD pathogenesis.

PMID:
24412367
PMCID:
PMC4329986
DOI:
10.1016/j.celrep.2013.12.029
[Indexed for MEDLINE]
Free PMC Article

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