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Mechanisms of itch in atopic dermatitis and prurigo: role of IL-31 from macrophages

Research Project

Project/Area Number 19K08743
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionNational Defense Medical College

Principal Investigator

Hashimoto Takashi  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、共同利用研究施設、病院並びに防衛, 病院 皮膚科, 講師 (00647844)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords痒み / アトピー性皮膚炎 / 痒疹 / マクロファージ / IL-31 / かゆみ
Outline of Research at the Start

本研究ではMoに注目し、(1) アトピー性皮膚炎および痒疹モデルマウスを用いたMoのIL-31 産生能の確認、(2) Mo由来のIL-31による痒み惹起能の確認、(3) ヒトのアトピー性皮膚炎および痒疹におけるMoのIL-31 産生能および産生促進因子の確認、を軸に慢性皮膚アレルギー疾患の痒みにおけるMoと IL-31 との関連を解明することにより、治療方法の開発につなげることを目的とする。

Outline of Final Research Achievements

Itch is a major problem in atopic dermatitis and prurigo. IL-31, which is a cytokine produced under allergic inflammation, plays a role in itch, but their cellular origins are still uncertain. The current study revealed that IL-31 comes from not only T cells but also macrophages. In animal models, macrophage depletion resulted in attenuation of scratching behavior. In addition, blockade of IL-31 signaling improved scratching behavior. IL-31 from macrophages appears to play a role in itch of atopic dermatitis and prurigo.

Academic Significance and Societal Importance of the Research Achievements

IL-31の産生細胞ならびに産生メカニズムを解明することで、IL-31の産生を抑えることができる。また、IL-31が本当に痒みと関わっているか、ということを解明することで、IL-31が痒みの治療のターゲットとなることを証明できる。本研究では、免疫に必要なT細胞ではなく、マクロファージ、特にM2マクロファージが少なくとも部分的にはIL-31を産生していることを示した。マクロファージあるいはIL-31をターゲットとした治療方法を開発することで、

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (21 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Int'l Joint Research] Miami Itch Center, University of Miami(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Miami Itch Center, University of Miami(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Eruptive pruritic papular porokeratosis accompanied by eosinophilic and basophilic infiltrate with upregulation of epidermal CCL26/eotaxin‐3 and thymic stromal lymphopoietin2021

    • Author(s)
      Awatani Kayo、Hashimoto Takashi、Satoh Takahiro
    • Journal Title

      The Journal of Dermatology

      Volume: 48 Issue: 8

    • DOI

      10.1111/1346-8138.15949

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Linear porokeratosis with severe itch accompanied by lesional upregulation of interleukin 31, thymic stromal lymphopoietin, and periostin2021

    • Author(s)
      Hashimoto Takashi、Moriyama Yoshihiro、Satoh Takahiro
    • Journal Title

      European Journal of Dermatology

      Volume: 31 Issue: 4 Pages: 570-572

    • DOI

      10.1684/ejd.2021.4083

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periostin, an Emerging Player in Itch Sensation2021

    • Author(s)
      Hashimoto Takashi、Mishra Santosh K.、Olivry Thierry、Yosipovitch Gil
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 141 Issue: 10 Pages: 2338-2343

    • DOI

      10.1016/j.jid.2021.03.009

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Itch intensity in prurigo nodularis is closely related to dermal interleukin‐31, oncostatin M, IL‐31 receptor alpha and oncostatin M receptor beta2021

    • Author(s)
      Hashimoto Takashi、Nattkemper Leigh A.、Kim Hei Sung、Kursewicz Christina D.、Fowler Emilie、Shah Serena M.、Nanda Sonali、Fayne Rachel A.、Paolini John F.、Romanelli Paolo、Yosipovitch Gil
    • Journal Title

      Experimental Dermatology

      Volume: - Issue: 6 Pages: 804-810

    • DOI

      10.1111/exd.14279

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dermal Periostin: A New Player in Itch of Prurigo Nodularis2021

    • Author(s)
      Hashimoto T、Nattkemper L、Kim H、Kursewicz C、Fowler E、Shah S、Nanda S、Fayne R、Romanelli P、Yosipovitch G
    • Journal Title

      Acta Dermato Venereologica

      Volume: 101 Issue: 1 Pages: adv00375-adv00375

    • DOI

      10.2340/00015555-3702

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages2020

    • Author(s)
      Hashimoto Takashi、Kursewicz Christina Dorothy、Fayne Rachel Alison、Nanda Sonali、Shah Serena Maya、Nattkemper Leigh、Yokozeki Hiroo、Yosipovitch Gil
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 140 Issue: 4 Pages: 850-859.e3

    • DOI

      10.1016/j.jid.2019.09.012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Itchy body: Topographical difference of itch and scratching and C Nerve fibres2019

    • Author(s)
      Hashimoto Takashi、Yosipovitch Gil
    • Journal Title

      Experimental Dermatology

      Volume: 28 Issue: 12 Pages: 1385-1389

    • DOI

      10.1111/exd.14054

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Possible roles of basophils in chronic itch2019

    • Author(s)
      Hashimoto Takashi、Rosen Jordan D.、Sanders Kristen M.、Yosipovitch Gil
    • Journal Title

      Experimental Dermatology

      Volume: 28 Issue: 12 Pages: 1373-1379

    • DOI

      10.1111/exd.13705

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Itching for an answer: A review of potential mechanisms of scalp itch in psoriasis2019

    • Author(s)
      Leon Argentina、Rosen Jordan D.、Hashimoto Takashi、Fostini Anna C.、Paus Ralf、Yosipovitch Gil
    • Journal Title

      Experimental Dermatology

      Volume: 28 Issue: 12 Pages: 1397-1404

    • DOI

      10.1111/exd.13947

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pruritus in ordinary scabies: IL-31 from macrophages induced by overexpression of TSLP and periostin2019

    • Author(s)
      Hashimoto Takashi、Satoh Takahiro、Yokozeki Hiroo
    • Journal Title

      Allergy

      Volume: 印刷中 Issue: 9 Pages: 1727-1737

    • DOI

      10.1111/all.13870

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Itching as a systemic disease2019

    • Author(s)
      Hashimoto Takashi、Yosipovitch Gil
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 144 Issue: 2 Pages: 375-380

    • DOI

      10.1016/j.jaci.2019.04.005

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prurigo successfully treated with duloxetine hydrochloride.2018

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

      Australas J Dermatol.

      Volume: 印刷中 Issue: 3 Pages: 237-239

    • DOI

      10.1111/ajd.12996

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] IL-31, a major pruritogen in a mouse model of atopic dermatitis, is generated through the macrophage/TSLP/periostin axis.2021

    • Author(s)
      Hashimoto T, Satoh T.
    • Organizer
      The 46th Annual Meeting of the JSID.
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SY1-2アトピー性皮膚炎の痒み2021

    • Author(s)
      端本宇志
    • Organizer
      第85回日本皮膚科学会東京支部学術大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 痒疹の痒み 痒み発生機序の最新の知見と対処法2021

    • Author(s)
      端本宇志
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Macrophages are the major cellular sources of IL-31 in atopic dermatitis:a novel network of itch comprising TSLP, periostin, and basophils2020

    • Author(s)
      Takashi Hashimoto, Hiroo Yokozeki, Takahiro Satoh
    • Organizer
      45th Japanese Society for Investigative Dermatology Annual Meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Implications of dermal IL-31 from M2 macrophages in itch in murine models of atopic dermatitis2020

    • Author(s)
      Takashi Hashimoto, Takahiro Satoh
    • Organizer
      JSA/WAO Joint Congress in 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Overexpression of dermal IL-31 generated by M2 macrophages and itch in murine models of atopic dermatitis2019

    • Author(s)
      Takashi Hashimoto, Takahiro Satoh, Hiroo Yokozeki
    • Organizer
      10th World Congress of Itch
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mechanisms of itch in stasis dermatitis: Significant role of IL-31 from macrophages.2019

    • Author(s)
      Takashi Hashimoto, Christina Dorothy Kursewicz, Rachel Alison Fayne, Sonali Nanda, Serena Maya Shah,
    • Organizer
      10th World Congress of Itch
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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