critical role for mast cell Stat5 activity in skin inflammation

Tomoaki Ando, Wenbin Xiao, Peisong Gao, Siavash Namiranian, Kenji Matsumoto, Yoshiaki Tomimori, Hong Hong, Hirotaka Yamashita, Miho Kimura, Jun ichi Kashiwakura, Tissa R. Hata, Kenji Izuhara, Michael F. Gurish, Axel Roers, Nicholas M. Rafaels, Kathleen C. Barnes, Colin Jamora, Yuko Kawakami, Toshiaki Kawakami

Research output: Contribution to journalArticlepeer-review

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skindisease. 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 withhuman AD. Mast cell expression of PLC-β3 was inversely correlated with that of phospho-STAT5, and increased mast cells with high levels ofphospho-STAT5 were found in lesional skin of some AD patients. Therefore, STAT5 regulatory mechanisms in mast cells are important for AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)366-376
Number of pages11
JournalCell Reports
Volume6
Issue number2
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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