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

Research Project

Project/Area Number 25461719
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionNational 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
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords痒疹 / 好塩基球 / STAT6 / そう痒 / 好酸球 / 痒み / TSLP / ERK
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.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (34 results)

All 2015 2014 2013 2012 Other

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Acknowledgement Compliant: 2 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (8 results)

  • [Journal Article] Protective Role of STAT6 in Basophil-Dependent Prurigo-like Allergic Skin Inflammation.2015

    • Author(s)
      Hashimoto T, Satoh T, Yokozeki H
    • Journal Title

      The journal of immunology

      Volume: 未定 Issue: 10 Pages: 4631-40

    • DOI

      10.4049/jimmunol.1401032

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Eosinophilic pustular folliculitis clinically presenting as orofacial granuloma: successful treatment with indomethacin, but not ibuprofen.2015

    • Author(s)
      Ono K, Hashimoto T, Satoh T.
    • Journal Title

      Acta Derm venereal

      Volume: 95 Issue: 3 Pages: 361-362

    • DOI

      10.2340/00015555-1926

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fish collagen allergy: a pitfall of the prick-to-prick test with raw fish.2015

    • Author(s)
      Chikazawa S, Hashimoto T, Kobayashi Y, Satoh T.
    • Journal Title

      Br J Dermatol

      Volume: 173 Issue: 5 Pages: 1330-1331

    • DOI

      10.1111/bjd.13962

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Generalized pruritus in parimary sclerosing cholangitis- implications of histamine by lysophosphatidic acid.2015

    • Author(s)
      Hashimoto T, Satoh T.
    • Journal Title

      Br J Dermatol

      Volume: 173 Issue: 5 Pages: 1334-1336

    • DOI

      10.1111/bjd.13992

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] In vitro Amyloidogenic Peptides of Galectin-7: Possible Mechanism of Amyloidogenesis of Primary Localized Cutaneous Amyloidosis.2014

    • Author(s)
      Ono K, Fujimoto E, Fujimoto N, Akiyama M, Satoh T, Maeda H, Fujii N, Tajima S
    • Journal Title

      J Biol Chem.

      Volume: 289 Issue: 42 Pages: 29195-29207

    • DOI

      10.1074/jbc.m114.592998

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IgG/IgA pemphigus recognizing desmogleins 1 and 3 in a patient with Sjögren’s syndrome.2014

    • Author(s)
      Furuya A, Takahashi E, Ishii N, Hashimoto T, Satoh T
    • Journal Title

      Eur J Dermatol

      Volume: 24 Pages: 512-513

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kimura’s disease with prurigo lesions treated with systemic indomethacin.2014

    • Author(s)
      Hashimoto T, Satoh T, Furuya A, Kataoka N, Yokozeki H.
    • Journal Title

      J Eur Acad Dermatol Venereol

      Volume: 28 Issue: 9 Pages: 1260-1262

    • DOI

      10.1111/jdv.12339

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] A common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility2014

    • Author(s)
      Sakiyama, M. Matsuo, H. Shimizu, S. Chiba, T. Nakayama, A. Takada, Y. Nakamura, T. Takada, T. Morita, E. Naito, M. Wakai, K. Inoue, H. Tatsukawa, S. Sato, J. Shimono, K. Makino, T. Satoh, T. Suzuki, H. Kanai, Y. Hamajima, N. Sakurai, Y. Ichida, K. Shimizu, T. Shinomiya, N.
    • Journal Title

      Hum Cell

      Volume: 27(1) Issue: 1 Pages: 1-4

    • DOI

      10.1007/s13577-013-0081-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Using CD40 Ligand Expression to Detect Antigen-specific T Cells in Patients with Drug Eruptions.2013

    • Author(s)
      Higuchi T, Satoh T, Yokozeki H.
    • Journal Title

      Acta Derm Venereol.

      Volume: 94(1): Issue: 1 Pages: 86-7

    • DOI

      10.2340/00015555-1617

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acrosyringeal involvement of palmoplantar lesions of eosnophilic pustular folliculitis2013

    • Author(s)
      Satoh T, Ikeda H, Yokozeki H.
    • Journal Title

      Acta Derm Venereol

      Volume: 93 Issue: 1 Pages: 99-99

    • DOI

      10.2340/00015555-1372

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Close association between metal allergy and nail lichen planus: detection of causative metals in nail lesions2013

    • Author(s)
      Nishizawa A, Satoh T, Yokozeki H.
    • Journal Title

      J Eur Acad Derm Venereol

      Volume: 27 Issue: 2 Pages: 231-234

    • DOI

      10.1111/j.1468-3083.2012.04561.x

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Indomethacin inhibits eosinophil migration to prostaglandin D2: therapeutic potential of CRTH2 desensitization for eosinophilic pustular folliculitis2013

    • Author(s)
      Kataoka N, Satoh T, Hirai A, Saeki K, Yokozeki H.
    • Journal Title

      Immunology

      Volume: 140(1): Issue: 1 Pages: 78-86

    • DOI

      10.1111/imm.12112

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] α(1,3) fucosyltransferases-IV and VII are essential for initial recruitment of basophils in chronic allergic inflammation2013

    • Author(s)
      Saeki K, Satoh T, Yokozeki H.
    • Journal Title

      J Invest Dermatol

      Volume: 133(9): Issue: 9 Pages: 2161-9

    • DOI

      10.1038/jid.2013.160

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Verbalizing Extremes of the Visual Analogue Scale for Pruritus: A Consensus Statement.2012

    • Author(s)
      Furue M, Ebata T, Ikoma A, Takeuchi S, Kataoka Y, Takamori K, et al.
    • Journal Title

      Acta Derm Venereol

      Volume: 93 Issue: 2 Pages: 214-215

    • DOI

      10.2340/00015555-1446

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 痒疹の病態と痒み2015

    • Author(s)
      佐藤貴浩
    • Organizer
      第45回日本皮膚アレルギー・接触皮膚炎学会
    • Place of Presentation
      松江
    • Year and Date
      2015-12-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] Generalized pruritus provoked by lysophosphatidic acid-induced histamine in a patient with primary sclerosing cholangitis.2015

    • Author(s)
      Hashimoto T, Satoh T
    • Organizer
      8th World Congress of Itch
    • Place of Presentation
      Nara
    • Year and Date
      2015-09-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical characteristics and immunological mechanisms of chronic prurigo慢性痒疹の臨床病型と免疫学的背景2015

    • Author(s)
      佐藤貴浩
    • Organizer
      25th International Sympojium of Itch 第25回国際かゆみシンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2015-09-27
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 汎発性皮膚瘙痒症ガイドラインと今後の課題2015

    • Author(s)
      佐藤貴浩
    • Organizer
      第114回日本皮膚科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2015-05-31
    • Related Report
      2015 Annual Research Report
  • [Presentation] 動物モデルからみた痒疹の病態2015

    • Author(s)
      佐藤貴浩
    • Organizer
      第114回日本皮膚科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2015-05-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 皮膚アレルギー疾患の薬物療法―ステロイド外用薬の使い方―2014

    • Author(s)
      佐藤貴浩
    • Organizer
      第1回総合アレルギー講習会
    • Place of Presentation
      横浜
    • Year and Date
      2014-12-20
    • Related Report
      2014 Research-status Report
  • [Presentation] What is prurigo? –a mysterious disease with pruritic papules of unknown etiology-2014

    • Author(s)
      Satoh T
    • Organizer
      The 39th Annual Meeting of the Japanese Society for Investigative Dermatology,
    • Place of Presentation
      Osaka
    • Year and Date
      2014-12-14
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] アトピー性皮膚炎―基礎の側面からー2014

    • Author(s)
      佐藤貴浩
    • Organizer
      第44回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 好塩基球からみた痒疹の病態と治療2014

    • Author(s)
      佐藤貴浩
    • Organizer
      第44日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] Inhibition of STAT6 signals exacerbates IgE-mediated, basophil-dependent prurigo-like reactions.

    • Author(s)
      Hashimoto T, Satoh T, Yokozeki H
    • Organizer
      Internatinal Investigative Dermatology 2013
    • Place of Presentation
      Edinburgh
    • Related Report
      2013 Research-status Report
  • [Presentation] Indomethacin inhibits eosinophil migration to prostaglandin D2: Proposal of a mechanism of action for eosinophilic pustular folliculitis.

    • Author(s)
      Hirai A, Kataoka N, Satoh T, Yokozeki H.
    • Organizer
      Internatinal Investigative Dermatology 2013
    • Place of Presentation
      Edinburgh
    • Related Report
      2013 Research-status Report
  • [Presentation] Pathological etiology and therapeutic approaches for prurigo

    • Author(s)
      佐藤貴浩
    • Organizer
      国際かゆみシンポジウム
    • Place of Presentation
      大阪市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 慢性痒疹診療ガイドライン ガイドラインを読むシリーズー皮膚疾患ガイドラインー 編集 宮地良樹2015

    • Author(s)
      佐藤貴浩
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • Related Report
      2015 Annual Research Report
  • [Book] 透析患者の痒みの現状と薬の使い方について教えてください いまさら訊けない透析患者の薬剤の使い方 編著 加藤明彦2015

    • Author(s)
      佐藤貴浩
    • Total Pages
      4
    • Publisher
      中外医学社
    • Related Report
      2015 Annual Research Report
  • [Book] 虫刺症(ストロフルスを含む)今日の小児治療指針 第16版 総編集 水口 雅 市橋 光 崎山 弘2015

    • Author(s)
      佐藤貴浩
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2015 Annual Research Report
  • [Book] 1. スキンケア指導法 幼小児によくみられる皮膚疾患アトラスー鑑別と治療のポイントー 横関博雄 片山一朗 編2015

    • Author(s)
      佐藤貴浩
    • Total Pages
      3
    • Publisher
      医薬ジャーナル
    • Related Report
      2015 Annual Research Report
  • [Book] 老人性乾皮症・皮脂欠乏性湿疹 今日の治療指針―私はこうしているー2015監修 山口徹 北原光夫 総編集  福井次矢 高木誠 小室一成2015

    • Author(s)
      佐藤貴浩
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2015 Annual Research Report
  • [Book] 痒疹はどのようにしてできる?WHAT’S NEW IN 皮膚科学2014-2015 宮地良樹編2014

    • Author(s)
      佐藤貴浩
    • Total Pages
      2
    • Publisher
      メディカルレビュー社
    • Related Report
      2014 Research-status Report
  • [Book] 皮膚瘙痒症. 診療ガイドラインUP-TO-DATE 監修 門脇 孝, 小室一成, 宮地良樹2014

    • Author(s)
      佐藤貴浩
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2014 Research-status Report
  • [Book] 高齢者によくみられる皮膚疾患アトラス2013

    • Author(s)
      佐藤貴浩
    • Total Pages
      2
    • Publisher
      医薬ジャーナル
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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