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Pathological involvement of Schwann cells in cutaneous allergic diseases.

Research Project

Project/Area Number 20K08689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKindai University (2021-2022)
Kyoto University (2020)

Principal Investigator

Otsuka Atsushi  近畿大学, 医学部, 教授 (60582054)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords接触皮膚炎 / シュワン細胞 / 皮膚アレルギー疾患
Outline of Research at the Start

皮膚アレルギー疾患病態形成における末梢神経の関与が注目されている。皮膚末梢神経は神経軸索とその支持細胞であるシュワン細胞からなるが、これまでの研究は神経軸索にシュワン細胞が混在した状態での評価であった。シュワン細胞がケモカイン等を産生することを申請者はすでに見出しており、神経軸索とシュワン細胞を区別しその機能を解析することが重要である。本研究では、シュワン細胞特異的ノックアウトマウスとシュワン細胞特異的光刺激マウスを作成し、免疫細胞との相互作用を解析することで皮膚アレルギー疾患における病態形成への関与を明らかとする。

Outline of Final Research Achievements

The role of peripheral nerves in skin allergy diseases is gaining attention, with a focus on distinguishing nerve fibers and Schwann cells. Schwann cell-specific optogenetic mice were created for basic analysis, but in a contact dermatitis model, inflammation didn't differ from control mice. Single-cell RNA sequencing revealed subsets of Schwann cells in the epidermis.
In a Staphylococcus aureus-induced dermatitis model, many eosinophils infiltrated the skin, and RTX treatment revealed the importance of peripheral nerves and Schwann cells. Both produced chemokines, and TLR2 KO mice showed reduced inflammation with eosinophils and basophils being the main inflammatory cells. The direct impact of Schwann cells on skin allergy reactions remains unclear, but nerve fibers' contribution to inflammation is suggested. Future research will explore Schwann cells' potential involvement in skin diseases.

Academic Significance and Societal Importance of the Research Achievements

皮膚アレルギー疾患における末梢神経の役割を研究しました。神経軸索とシュワン細胞から成る末梢神経の解析に焦点を当て、シュワン細胞特異的光刺激マウスを作成し基礎的解析を行いました。接触皮膚炎の程度に差はありませんでしたが、シングルセルRNAシークエンスを用いてシュワン細胞の解析を行い、サブセットが存在することが分かりました。
黄色ブドウ球菌による皮膚炎モデルで、好塩基球が皮膚に浸潤することを確認し、神経軸索とシュワン細胞が炎症に関与する可能性が示唆されました。今後は、シュワン細胞が影響を与える皮膚疾患の可能性について検討し、皮膚アレルギー疾患の理解を深め、治療法の開発に寄与することが期待されます。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2022 2021

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Filaggrin-deficient rats generated using zinc-finger nucleases spontaneously exhibit dry scaly skin2022

    • Author(s)
      Nakashima Chisa、Doi Hiromi、Nakajima Saeko、Mashimo Tomoji、Oga Toru、Ishida-Yamamoto Akemi、Honda Tetsuya、Ishida Yoshihiro、Otsuka Atsushi、Kabashima Kenji
    • Journal Title

      Allergology International

      Volume: 71 Issue: 4 Pages: 545-547

    • DOI

      10.1016/j.alit.2022.04.001

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors2022

    • Author(s)
      Nakashima Chisa、Yanagihara Shigeto、Otsuka Atsushi
    • Journal Title

      Allergology International

      Volume: 71 Issue: 1 Pages: 40-46

    • DOI

      10.1016/j.alit.2021.10.004

    • NAID

      130008145235

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2021 Research-status Report
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide promotes cutaneous dendritic cell functions in contact hypersensitivity.2021

    • Author(s)
      Yasuo Yamamoto 1, Atsushi Otsuka 2, Yoshihiro Ishida 3, Lai San Wong 4, Judith A Seidel 3, Yumi Nonomura 3, Chisa Nakashima 3, Saeko Nakajima 3, Akihiko Kitoh 3, Takashi Nomura 3, Teruki Dainichi 3, Tetsuya Honda 3, Wataru Amano 1, Noriko Konishi 5, Mikio Hayashi 5, Mutsuyoshi Matsushita 5, Kenji Kabashima 6
    • Journal Title

      J Allergy Clin Immunol.

      Volume: 18;S0091-6749(21) Issue: 3 Pages: 00218-9

    • DOI

      10.1016/j.jaci.2021.02.005

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prolonged high-intensity exercise induces fluctuating immune responses to herpes simplex virus infection via glucocorticoids2021

    • Author(s)
      Adachi, A., Honda, T., Dainichi, T., Egawa, G., Yamamoto, Y., Nomura, T., Nakajima, S., Otsuka, A., Maekawa, M., Mano, N., Koyanagi, N., Kawaguchi, Y., Ohteki, T., Nagasawa, T., Ikuta, K., Kitoh, A., and Kabashima, K.
    • Journal Title

      J. Allergy Clin. Immunol.

      Volume: 148 Issue: 6 Pages: 1575-1588.e7

    • DOI

      10.1016/j.jaci.2021.04.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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