Analysis of immunological mechanisms and therapeutic approach for prurigo, itch, and other pruritic skin diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461719
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: National Defense Medical College
• Principal Investigator: Satoh Takahiro 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 医学教育部医学科専門課程, 教授 (30235361)
• Co-Investigator(Renkei-kenkyūsha): HASHIMOTO Takashi 東京医科歯科大学, 大学院医歯学総合研究科・皮膚科学分野, 助教 (00647844) ; FURUYA Aiko 済生会川口病院, 皮膚科, 医師 (30622972)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 痒疹 / 好塩基球 / STAT6 / そう痒 / 好酸球

Outline of Final Research Achievements

We established a mouse model of prurigo. Skin lesions were characterized by irregular acanthosis and dermal eosinophils, mononuclear cells, and basophils, with epidermal nerve fiber sprouting. In vivo depletion of basophils alleviated skin reactions. Unexpectedly, deficiency of STAT6 caused exacerbation of skin inflammation. Notably, decreased scratching behaviors were associated with reduced tissue eosinophils, despite exacerbated inflammation. We also analyzed human prurigo patients. Epidermal keratinocytes expressed TLSP and IL-33 in all groups. There was no close association between prurigo and malignancy or metal allergy. In a patient with pruritus cutaneus due to sclerosing cholangitis, serum levels of autotaxin , a synthetic enzyme for lysophosphatidic acid (LPA), and histamine correlated with pruritus. Blood cells produced histamine in response to LPA in vitro. Thus, LPA appeared to contribute to cholestatic pruritus via stimulating basophils to produce histamine.

Free Research Field

皮膚科学