TH2 cytokines increase kallikrein 7 expression and function in patients with atopic dermatitis

• Published in: Journal of allergy and clinical immunology Vol. 130; no. 1; pp. 259 - 261.e1
• Main Authors: Morizane, Shin, Yamasaki, Kenshi, Kajita, Ai, Ikeda, Kazuko, Zhan, Maosheng, Aoyama, Yumi, Gallo, Richard L., Iwatsuki, Keiji
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2012; Elsevier; Elsevier Limited
• Subjects: Allergic diseases; Biological and medical sciences; Cells, Cultured; Cytokines - immunology; Dermatitis, Atopic - immunology; Dermatitis, Atopic - physiopathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Humans; Immunopathology; Interleukin-13 - immunology; Interleukin-4 - immunology; Kallikreins - genetics; Kallikreins - metabolism; Keratinocytes - immunology; Keratinocytes - metabolism; Medical sciences; Pathogenesis; Permeability; Proteases; Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin allergic diseases. Stinging insect allergies; Statistical analysis; Th2 Cells - immunology; Up-Regulation; Human; Allergy; Immunopathology; Skin disease; Immunology; Atopic dermatitis; Cytokine; T-Lymphocyte; Kallikrein; Increase; Th2 lymphocyte; Atopy
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.03.006

To the Editor: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disorder characterized by a TH2 environment and epidermal barrier dysfunction.1,2 A primary defect in the epidermal barrier has been proposed as the initial event in the development of AD because loss-of-function mutations in the filaggrin gene are associated with AD.2 Excessive protease activity is another characteristic abnormality affecting the epidermal barrier in patients with AD. TH2 cytokines are generally expressed by TH2 lymphocytes, basophils, eosinophils, and mast cells and play roles in TH2 cell differentiation, IgE production, eosinophil recruitment, and so forth.1 These cytokines also affect epidermal barrier functions through signal transducer and activator of transcription 6 because IL-4 and IL-13 decrease the expression of filaggrin, loricrin, and involucrin in keratinocytes.5 Hatano et al6 reported that IL-4 suppresses the expression of ceramide and cutaneous permeability barrier functions induced by TNF-α and IFN-γ and the recovery of cutaneous permeability barrier dysfunction in vivo.5 Desmoglein 3 expression is also inhibited by IL-4.5 IL-4 transgenic mice spontaneously have AD-like dermatitis, which supports the importance of TH2 cytokines in AD pathogenesis.1 We here report how TH2 cytokines could further alter the skin barrier by showing that IL-4 and IL-13 increase KLK7 expression and function in keratinocytes.