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New concept of the pathogenesis of atopic dermatitis: Interplay among the barrier, allergy, and pruritus as a trinity

  • Kenji Kabashima
    Correspondence
    Correspondence address: Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawara, Sakyo, Kyoto 606-8507, Japan. Tel.: +81 75 751 3310; fax: +81 75 761 3002.
    Affiliations
    Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
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      Abstract

      Atopic dermatitis (AD) is a common skin condition, characterized by a complex, heterogeneous pathogenesis, including skin barrier dysfunctions, allergy/immunology, and pruritus. When the skin barrier is disrupted by, for example, the filaggrin gene mutation and/or environmental factors, the skin is predisposed to being penetrated by external stimuli. Foreign antigens can be subdivided into two subsets by size: haptens (including metals) and protein antigens. It is known that a single hapten challenge provokes Th1 initially, but that repeated elicitation with haptens results in a shift toward Th2-dominated responses. On the other hand, exposure to protein antigens directly induces Th2-dominant conditions via the thymic stromal lymphopoietin (TSLP) receptor on Langerhans cells. Recently, it has been revealed that Th2 cells produce IL-31, which provokes pruritus, and that Th2 cytokines decrease filaggrin expressions by keratinocytes. These findings suggest that Th2 conditions lead to pruritus and barrier dysfunctions. In this review, we will examine the highly complex interplay among skin barrier abnormality, allergy/immunology, and pruritus as a trinity in the development of AD.

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      Biography

      Kenji Kabashima received the MD from Kyoto University in 1996. After the internship at the United State Naval Hospital in Yokosuka, Japan, and residency at University of Washington, USA, he received the PhD from Kyoto University in 2003. He was assigned as an assistant professor at the Department of Dermatology, Kyoto University (2003), a research associate at the Department of Microbiology and Immunology, UCSF (2003–2005), an associate professor at the Department of Dermatology at UOEH (2005–2008), and an associate professor at the Department of Dermatology, Kyoto University. His interests are cutaneous immunology, live imaging of the skin, and lipid biology. His hobbies are mountaineering, marathon, and blogging.