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Analysis of histamine production in sweat glands and its pathogenic roles in skin allergic diseasel

Research Project

Project/Area Number 21K08302
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionHiroshima University

Principal Investigator

Takahagi Shunsuke  広島大学, 医系科学研究科(医), 准教授 (40448246)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords汗腺 / ヒスタミン / IL-1 / コリン性蕁麻疹 / アトピー性皮膚炎 / 発汗時の皮膚の疼痛
Outline of Research at the Start

発汗はアトピー性皮膚炎やコリン性蕁麻疹を悪化させる。驚くべき事にヒト汗中にはアレルギー物質であるヒスタミンが高濃度に含まれるが、その由来は知られていない。本研究では、汗中のヒスタミンの産生源として汗腺に着目し、汗腺細胞におけるヒスタミン産生能、および産生したヒスタミンの汗中への分泌機構を解析する。また、その機序を抑制する物質を探索することで皮膚アレルギーの新しい治療薬を見いだす。

Outline of Final Research Achievements

Histidine decarboxylase (HDC) protein, a histamine-producing enzyme, was detected in human and mouse skin sweat glands. Mouse sweat glands also expressed the HDC gene in in-vitro experiments. Culture of sweat glands in extracellular matrix induced histamine production in the culture supernatant and extracellular matrix, indicating that sweat glands have histamine-producing capacity. In addition, genes involved in histamine metabolism and transport were detected in mouse sweat glands, and HDC expression was enhanced by cytokine stimulation. IL-1, a proinflammatory cytokine in sweat, was also produced in mouse sweat glands and its expression was increased via a receptor signaling. This study suggests that mouse sweat glands produce proinflammatory mediators such as histamine and IL-1, and may be associated with the pathogenesis of sweat-related cutaneous allergic diseases.

Academic Significance and Societal Importance of the Research Achievements

これまで皮膚アレルギー領域において、ヒスタミン産生細胞として好塩基球と肥満細胞が広く知られてきたが、本研究ではこれらの細胞以外に皮膚に備わる付属器からもヒスタミンが産生されうることを示した。また、汗腺がヒスタミンやIL-1の炎症性メディエータを産生することは、これらのメディエータの産生抑制や阻害は、発汗と関連する皮膚アレルギー疾患の新しい治療薬の開発につながる可能性がある。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Propylthiouracil-induced Alopecia Accompanying Hypohidrosis and Onychomadesis2022

    • Author(s)
      Yanagida N, Takahagi S, Tanaka A, Hide M
    • Journal Title

      Acta Derm Venereol

      Volume: 102 Pages: adv00763-adv00763

    • DOI

      10.2340/actadv.v102.2690

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunological Changes of Basophil Hyperreactivity to Sweat in Patients With Well-Controlled Atopic Dermatitis2022

    • Author(s)
      Numata Tomofumi、Takahagi Shunsuke、Ishii Kaori、Morioke Satoshi、Kan Takanobu、Mizuno Hayato、Yanase Yuhki、Kawaguchi Tomoko、Tanaka Akio、Hide Michihiro
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 883605-883605

    • DOI

      10.3389/fimmu.2022.883605

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A survey on subtypes and clinical characteristics of 1061 patients with urticaria in the primary care institutes in Japan2022

    • Author(s)
      Saito R, Takahagi S, Nakano F, Furutani K, Mihara S, Numata T, Kameyoshi Y, Tanaka T, Shindo H, Niimi N, Iwamoto K, Hiragun T, Hiragun M, Tanaka A, Hide M
    • Journal Title

      J Dermatol

      Volume: 49 Issue: 12 Pages: 1255-1262

    • DOI

      10.1111/1346-8138.16562

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical and histological characterization of transient dermal pain triggered by sweating stimuli.2022

    • Author(s)
      Takahagi S, Okamoto M, Ishii K, Tanaka A, Mizuno H, Harada N, Yanagida N, Hide M.
    • Journal Title

      Allergol Int.

      Volume: In press

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anhidrosis accompanied with cholinergic urticaria-like rash and dermal pain in a patient with Sjogren’s syndrome.2022

    • Author(s)
      Yanagida N, Takahagi S, Aoyama Y, Tanaka A, Hide M.
    • Journal Title

      J Dermatol.

      Volume: In press

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 無汗部位と異なる範囲に疼痛を生じた特発性後天性全身性無汗症の1例.2021

    • Author(s)
      水野隼登, 高萩俊輔, 岡本真由美, 秀 道広.
    • Journal Title

      発汗学

      Volume: 28 Pages: 31-33

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【アトピー性皮膚炎のスキンケア】アトピー性皮膚炎では汗の減少と感染症はどのように関連しているのか?.2021

    • Author(s)
      沼田智史, 高萩俊輔, 秀 道広.
    • Journal Title

      美容皮膚科

      Volume: 4 Pages: 33-41

    • Related Report
      2021 Research-status Report
  • [Presentation] 蕁麻疹の診断と治療2023

    • Author(s)
      高萩俊輔
    • Organizer
      第5回日本アレルギー学会中国・四国地方会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Recent progress in understanding and managing urticaria2022

    • Author(s)
      Shunsuke Takahagi
    • Organizer
      The 12th Asian Dermatological Congress
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 全身性の乏汗と爪甲脱落症を伴った薬剤性円形脱毛症の1例2022

    • Author(s)
      高萩俊輔、栁田のぞみ、田中暁生、秀 道広
    • Organizer
      第30回日本発汗学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Review and perspective of allergic skin diseases associated with sweating2021

    • Author(s)
      Takahagi S
    • Organizer
      2021 GA2LEN UCARE Urticaria Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 特発性分節性無汗症の1例2021

    • Author(s)
      森田智子, 玉理紗帆, 栁田のぞみ, 高萩俊輔, 亀頭晶子
    • Organizer
      第149回日本皮膚科学会広島地方会
    • Related Report
      2021 Research-status Report
  • [Presentation] イントロダクション「発汗障害と皮膚の疼痛」2021

    • Author(s)
      高萩俊輔
    • Organizer
      第29回日本発汗学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 発汗刺激時にコリン性蕁麻疹様皮疹と皮膚の疼痛を呈したシェーグレン症候群の1例2021

    • Author(s)
      栁田のぞみ, 高萩俊輔, 田中暁生, 秀 道広
    • Organizer
      第29回日本発汗学会総会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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