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How do tissue resident memory T cells induce the local recurrence of atopic dermatitis

Research Project

Project/Area Number 18K08297
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MURATA Akihiko  鳥取大学, 医学部, 助教 (90624221)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords組織常在性記憶T細胞 / ヘルパーT細胞 / アトピー性皮膚炎 / 接触性皮膚炎 / 皮膚局所の免疫記憶 / 接触過敏症 / 表皮gamma-delta T細胞
Outline of Final Research Achievements

In this study, we investigated the mechanism of repeated relapses and remissions of allergic skin diseases such as atopic dermatitis in the same area using a mouse model of dermatitis. We found that in addition to killer T cells, a large number of helper T cells remained in the dermis as memory T cells in the inflammation-healed skin. Each of these memory T cells formed 'local skin immune memory' and locally increased reactivity to allergens of the skin. Moreover, while memory killer T cells disappeared from the inflammation-experienced skin within 1 year after healing, memory helper T cells continued to be maintained during this period. Thus, these results indicate that helper memory T cells, which remain in the inflammation-experienced skin, are one of the cause of the recurrence of inflammatory skin diseases.

Academic Significance and Societal Importance of the Research Achievements

本研究から、炎症を経験した皮膚に形成される局所の免疫記憶は、皮膚に留まり続ける記憶ヘルパーT細胞が長期間維持することが分かった。よって、炎症性皮膚疾患の再発を根治するためには、患部から記憶ヘルパーT細胞を除去することで皮膚局所の免疫記憶を解消する必要があると示唆された。ステロイド剤の塗布等による治療では、症状が改善しても塗布を中止するとしばしば同じ部位で再発することから、既存の方法では皮膚局所の免疫記憶は除去できないと考えられる。今後、本研究の成果を元に、皮膚で記憶ヘルパーT細胞が維持される仕組みが明らかになり、その分子機構を標的とした皮膚疾患再発の根本治療法が開発されることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (7 results) Remarks (7 results)

  • [Journal Article] 常在生記憶ヘルパーT細胞が担う皮膚の局所的な長期免疫記憶2021

    • Author(s)
      村田暁彦
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 75 Pages: 292-298

    • Related Report
      2020 Annual Research Report
  • [Journal Article] CD4+-resident memory T cells mediate long-term local skin immune memory of contact hypersensitivity in BALB/c mice2020

    • Author(s)
      Akihiko Murata, Shin-Ichi Hayashi
    • Journal Title

      Frontiers in Immunology

      Volume: in press Pages: 775-775

    • DOI

      10.3389/fimmu.2020.00775

    • NAID

      120007170662

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Local injection of CCL19-expressing mesenchymal stem cells augments the therapeutic efficacy of anti-PD-L1 antibody by promoting infiltration of immune cells2020

    • Author(s)
      Iida Yuichi、Yoshikawa Rintaro、Murata Akihiko、Kotani Hitoshi、Kazuki Yasuhiro、Oshimura Mitsuo、Matsuzaki Yumi、Harada Mamoru
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 8 Issue: 2 Pages: e000582-e000582

    • DOI

      10.1136/jitc-2020-000582

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of miR-669m inhibits erythroblast differentiation2020

    • Author(s)
      Kotaki R., et.al. Kawashima M, Yamaguchi A, Suzuki N, Koyama-Nasu R, Ogiya D, Okuyama K, Yamamoto Y, Takamatsu M, Kurosaki N, Ando K, Murata A, Ohtsuka M, Nakagawa S, Katagiri K, Kotani A.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 13554-13554

    • DOI

      10.1038/s41598-020-70442-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiple developmental pathways lead to the generation of CD4 T-cell memory2020

    • Author(s)
      Hojyo Shintaro、Tumes Damon、Murata Akihiko、Tokoyoda Koji
    • Journal Title

      International Immunology

      Volume: 32 Issue: 9 Pages: 589-595

    • DOI

      10.1093/intimm/dxaa051

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Notchによるマスト細胞の接着2019

    • Author(s)
      村田暁彦,林眞一
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 71 Pages: 576-582

    • Related Report
      2019 Research-status Report
  • [Journal Article] Kit-independent mast cell adhesion mediated by Notch2019

    • Author(s)
      Akihiko Murata, Mari Hikosaka, Miya Yoshino, Lan Zhou, Shin-Ichi Hayashi
    • Journal Title

      International Immunology

      Volume: 31 Issue: 2 Pages: 69-79

    • DOI

      10.1093/intimm/dxy067

    • NAID

      120007170663

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 接触過敏症における皮膚局所の免疫記憶2018

    • Author(s)
      村田暁彦, 林眞一
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 70 Pages: 367-372

    • Related Report
      2018 Research-status Report
  • [Presentation] CD4+ and CD8+ resident memory T cells redundantly mediate local skin memory response in contact dermatitis.2019

    • Author(s)
      Murata A, Yoshino M, Hayashi SI
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Influence of immune activation on the transport of skin self-antigens to regional lymph nodes.2019

    • Author(s)
      Yoshino M, Murata A, Hayashi SI
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Local deliver of CCL19-expressing mesenchymal stromal cells augments the therapeutic efficacy by anti-PD-L1 blockade antibody via promoting infiltration of immune cells.2019

    • Author(s)
      Iida Y, Yoshikawa R, Murata A, Kotani H, Harada M
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Local skin memory response is mediated by tissue resident memory T cells2018

    • Author(s)
      Akihiko Murata, Miya Yoshino, Shin-Ichi Hayashi
    • Organizer
      第47回日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Distinct effect of LPS stimulation on TLR3 expression in macrophage subsets2018

    • Author(s)
      Kazune Tanigawa, Akihito Murata, Miya Yoshino, Shin-Ichi Hayashi
    • Organizer
      第47回日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Analysis of the transport of self-antigens from the skin to regional LNs under inflammatory conditions2018

    • Author(s)
      Miya Yoshino, Kazune Tanigawa, Akihiko Murata, Shin-Ichi Hayashi
    • Organizer
      第47回日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Local delivery of CCL19-expressing mesenchymal stromal cells suppresses the tumor growth via promoting infiltration of immune cells2018

    • Author(s)
      Yuichi Iida, Rintaro Yoshikawa, Akihiko Murata, Yumi Matsuzaki, Mamoru Harada
    • Organizer
      第47回日本免疫学会
    • Related Report
      2018 Research-status Report
  • [Remarks] 鳥取大学医学部プレスリリース 皮膚炎の免疫記憶細胞を同定

    • URL

      https://www.med.tottori-u.ac.jp/files/42351.pdf

    • Related Report
      2020 Annual Research Report
  • [Remarks] 鳥取大学医学部生命科学科 論文掲載情報

    • URL

      https://www.med.tottori-u.ac.jp/files/41419.pdf

    • Related Report
      2019 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科 論文掲載情報

    • URL

      https://www.med.tottori-u.ac.jp/introduction/lifesciences/life-science.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科 論文掲載情報

    • URL

      https://www.med.tottori-u.ac.jp/introduction/lifesciences/873/921/26014.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科 論文掲載情報(NotchによるKit非依存的なマスト細胞の接着機構の発見)

    • URL

      https://www.med.tottori-u.ac.jp/introduction/lifesciences/873/murata_20181113.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科 論文掲載情報(接触過敏症における皮膚局所の免疫記憶)

    • URL

      https://www.med.tottori-u.ac.jp/introduction/lifesciences/873/201810_murata.html

    • Related Report
      2018 Research-status Report
  • [Remarks] 鳥取大学医学部生命科学科分子細胞生物学講座免疫学分野 業績欄

    • URL

      https://www.med.tottori-u.ac.jp/immunol/307/1371.html

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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