Volume 6, Issue 2, p366–376, 30 January 2014
Ando T1, Xiao W1, Gao P2, Namiranian S3, Matsumoto K4, Tomimori Y1, Hong H1, Yamashita H1, Kimura M1, Kashiwakura J5, Hata TR6, Izuhara K7, Gurish MF8,Roers A9, Rafaels NM2, Barnes KC2, Jamora C3, Kawakami Y1, Kawakami T10
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.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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