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Immune systems involved in the resolution of inflammation and tissue repair

Research Project

Project/Area Number 17H06175
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionKeio University

Principal Investigator

YOSHIMURA Akihiko  慶應義塾大学, 医学部(信濃町), 教授 (90182815)

Project Period (FY) 2017-05-31 – 2022-03-31
Project Status Discontinued (Fiscal Year 2021)
Budget Amount *help
¥205,790,000 (Direct Cost: ¥158,300,000、Indirect Cost: ¥47,490,000)
Fiscal Year 2021: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2020: ¥38,220,000 (Direct Cost: ¥29,400,000、Indirect Cost: ¥8,820,000)
Fiscal Year 2019: ¥40,560,000 (Direct Cost: ¥31,200,000、Indirect Cost: ¥9,360,000)
Fiscal Year 2018: ¥48,620,000 (Direct Cost: ¥37,400,000、Indirect Cost: ¥11,220,000)
Fiscal Year 2017: ¥51,870,000 (Direct Cost: ¥39,900,000、Indirect Cost: ¥11,970,000)
Keywords免疫制御 / マクロファージ / 制御性T細胞 / 神経炎症 / 組織修復 / 免疫学 / 脳神経 / シグナル伝達 / 生体分子 / 生理活性 / 炎症 / 免疫 / アレルギー・喘息 / 細胞・組織 / 獲得免疫 / 慢性炎症 / 脳梗塞 / 組織損傷 / 創傷治癒 / アストロサイト / 神経症状 / 脳・神経
Outline of Final Research Achievements

We have elucidated the immune mechanisms involved in inflammation and tissue repair induced by organ damage, focusing on a mouse model of cerebral infarction. Inflammation occurs in the acute phase within one day after stroke, resulting in worsening of symptoms, but inflammation begins to subside on the third day or later. They found that macrophages and scavenger receptors expressed on the surface of macrophages are involved in this process. Furthermore, they found that a large number of regulatory T cells accumulate in the brain during the chronic phase after the second week of disease onset and contribute to the recovery of neurological symptoms by suppressing the excessive activation of microglia and astrocytes.

Academic Significance and Societal Importance of the Research Achievements

ヒト脳梗塞とTregの関連を示唆する報告は多い。例えばヒト脳梗塞において末梢血のTregの数と予後の関係が報告されている。セロトニントランスポーター阻害剤(SSRI)は脳梗塞患者の神経症状を改善することが複数報告されている。したがってヒト脳梗塞慢性期においても脳Tregが神経修復に働いている可能性はある。腎傷害モデルにおいてもやはり慢性期にTreg が腎臓に集積し腎機能回復を促進していることを我々は報告している。組織に浸潤するTregは炎症の収束のみならず組織修復にも重要な役割があることが示された。さらに組織特異的なTregを用いた組織特異的な治療法の開発につながることが期待される。

Assessment Rating
Verification Result (Rating)

A

Assessment Rating
Result (Rating)

A: Progress in the research is steadily towards the initial goal. Expected research results are expected.

Report

(10 results)
  • 2022 Research Progress Assessment (Verification Result) ( PDF )
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Abstract ( PDF )   Comments on the Screening Results ( PDF )   Annual Research Report
  • Research Products

    (35 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (13 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (12 results) (of which Int'l Joint Research: 8 results,  Invited: 11 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Central South University(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] La Jolla Institute for Immunology(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] La Jolla Institute for Immunology(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Friedrich-Alexander-University(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Central South University(中国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] La Jolla Institute for Immunology(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Regulation of peripheral Th/Treg differentiation and suppression of airway inflammation by Nr4a transcription factors.2021

    • Author(s)
      Takashi Sekiya, Shizuko Kagawa, Katsunori Masaki, Koichi Fukunaga, Akihiko Yoshimura, Satoshi Takaki .
    • Journal Title

      iScience.

      Volume: 24 Issue: 3 Pages: 102166-102166

    • DOI

      10.1016/j.isci.2021.102166

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRIM28 Expression on Dendritic Cells Prevents Excessive T Cell Priming by Silencing Endogenous Retrovirus2021

    • Author(s)
      Chikuma Shunsuke、Yamanaka Soichiro、Nakagawa So、Ueda Mahoko Takahashi、Hayabuchi Hodaka、Tokifuji Yukiko、Kanayama Masashi、Okamura Tadashi、Arase Hisashi、Yoshimura Akihiko
    • Journal Title

      The Journal of Immunology

      Volume: 206 Issue: 7 Pages: 1528-1539

    • DOI

      10.4049/jimmunol.2001003

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tocilizumab monotherapy uncovered the role of the CCL22/17-CCR4+ Treg axis during remission of crescentic glomerulonephritis2020

    • Author(s)
      Sakai R, Ito M, Yoshimoto K, Chikuma S, Kurasawa T, Kondo T, Suzuki K, Takeuchi T, Amano K, Yoshimura A
    • Journal Title

      Clin Transl Immunology

      Volume: 9 Issue: 11

    • DOI

      10.1002/cti2.1203

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury.2020

    • Author(s)
      Sakai R, Ito M, Komai K, Iizuka-Koga M, Matsuo K, Nakayama T, Yoshie O, Amano K, Nishimasu H, Nureki O, Kubo M, Yoshimura A.
    • Journal Title

      Cell Mol Immunol.

      Volume: Sep Issue: 5 Pages: 11-11

    • DOI

      10.1038/s41423-020-00547-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The liver-brain-gut neural arc maintains the Treg cell niche in the gut2020

    • Author(s)
      Teratani T, Mikami Y, Nakamoto N, Suzuki T, Harada Y, Okabayashi K, Hagihara Y, Taniki N, Kohno K, Sibata S, Miyamoto K, Ishigame H, Chu Po-Sung, Sujino T, Suda W, Hattori M, Matsui M, Okada T, Okano H, Inoue M, Yada T, Kitagawa Y, Yoshimura A, Tanida M, Tsuda M, Iwasaki Y, Kanai T.
    • Journal Title

      Nature

      Volume: 585 Issue: 7826 Pages: 591-596

    • DOI

      10.1038/s41586-020-2425-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD.2020

    • Author(s)
      Imura Y, Ando M, Kondo T, Ito M, Yoshimura A.
    • Journal Title

      JCI Insight.

      Volume: 23;5(14) Issue: 14

    • DOI

      10.1172/jci.insight.136185

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TGF-β-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis.2020

    • Author(s)
      Dees C, Potter S, Zhang Y, Bergmann C, Zhou X, Luber M, Wohlfahrt T, Karouzakis E, Ramming A, Gelse K, Yoshimura A, Jaenisch R, Distler O, Schett G, Distler JH.
    • Journal Title

      J Clin Invest.

      Volume: 印刷中 Issue: 5 Pages: 2347-2363

    • DOI

      10.1172/jci122462

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery2019

    • Author(s)
      Ito Minako、Komai Kyoko、Mise-Omata Setsuko、Iizuka-Koga Mana、Noguchi Yoshiko、Kondo Taisuke、Sakai Ryota、Matsuo Kazuhiko、Nakayama Takashi、Yoshie Osamu、Nakatsukasa Hiroko、Chikuma Shunsuke、Shichita Takashi、Yoshimura Akihiko
    • Journal Title

      Nature

      Volume: 565 Issue: 7738 Pages: 246-250

    • DOI

      10.1038/s41586-018-0824-5

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tissue regulatory T cells and neural repair.2019

    • Author(s)
      Ito M, Komai K, Nakamura T, Srirat T, Yoshimura A.
    • Journal Title

      Int Immunol.

      Volume: Mar 20. pii: dxz031. Issue: 6 Pages: 361-369

    • DOI

      10.1093/intimm/dxz031

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NR4A transcription factors limit CAR T cell function in solid tumours2019

    • Author(s)
      Chen Joyce、L?pez-Moyado Isaac F.、Seo Hyungseok、Lio Chan-Wang J.、Hempleman Laura J.、Sekiya Takashi、Yoshimura Akihiko、Scott-Browne James P.、Rao Anjana
    • Journal Title

      Nature

      Volume: 567 Issue: 7749 Pages: 530-534

    • DOI

      10.1038/s41586-019-0985-x

    • Related Report
      2019 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization, and IL-17 expression.2019

    • Author(s)
      Nakatsukasa H, Oda M, Yin J, Chikuma S, Ito M, Koga-Iizuka M, Someya K, Kitagawa Y, Ohkura N, Sakaguchi S, Koya I, Sanosaka T, Kohyama J, Tsukada YI, Yamanaka S, Takamura-Enya T, Lu Q, Yoshimura A
    • Journal Title

      International immunology

      Volume: 31 Issue: 5 Pages: 335-347

    • DOI

      10.1093/intimm/dxz008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pulmonary phagocyte-derived NPY controls the pathology of severe influenza virus infection.2018

    • Author(s)
      Fujiwara S., Hoshizaki M., Ichida Y., Lex D., Kuroda E., Ishii KJ., Magi S., Okada M., Takao H., Gando M., Imai H., Hara R., Herzog H., Yoshimura A., Okamura H., Penninger JM., Slutsky AS., Uhlig S., Kuba K., and Imai Y.
    • Journal Title

      Nature Microbiology

      Volume: 4(2) Issue: 2 Pages: 258-268

    • DOI

      10.1038/s41564-018-0289-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nr4a Receptors Regulate Development and Death of Labile Treg Precursors to Prevent Generation of Pathogenic Self-Reactive Cells2018

    • Author(s)
      Takashi Sekiya、Hibino Sana、Saeki Keita、Kanamori Mitsuhiro、Takaki Satoshi、Yoshimura Akihiko
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 6 Pages: 1627-1638.e6

    • DOI

      10.1016/j.celrep.2018.07.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Molecular mechanism of T cell exhaustion by NR4a nuclear receptors and its reversion2020

    • Author(s)
      Akihiko Yoshimura
    • Organizer
      第24回日本がん免疫学会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] cAMPを介した免疫制御の分子機構2020

    • Author(s)
      吉村昭彦
    • Organizer
      第41回日本炎症・再生医学会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural Damage and Repair after Ischemic Brain Injury by Innate and Adaptive Immunity2020

    • Author(s)
      Akihiko Yoshimura
    • Organizer
      The 9th NIF Winter School on Advanced Immunology in Awaji Island
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural Repair after ischemic brain injury by Regulatory T cells2019

    • Author(s)
      Akihiko Yoshimura, Takashi Schichita and Minako Ito
    • Organizer
      NCNP Neuroimmunology international symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural Repair after Ischemic Brain Injury by Regulatory T cells2019

    • Author(s)
      Minako Ito, Takashi Shichita, Akihiko Yoshimura
    • Organizer
      2019, Chinese Society of Immunology
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulation of inflammation after ischemic brain injury by innate and adaptive immunity2019

    • Author(s)
      Minako Ito, Akihiko Yoshimura
    • Organizer
      the 9th international DAMPs and Alarmin Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neural Repair after Ischemic Brain Injury2019

    • Author(s)
      Minako Ito, Akihiko Yoshimura
    • Organizer
      the 14th World Congress on Inflammation
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 制御性T細胞による炎症疾患制御2018

    • Author(s)
      吉村昭彦
    • Organizer
      第52回日本眼炎症学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 組織制御性T細胞(Tissue-Treg)による組織損傷の修復2018

    • Author(s)
      吉村昭彦
    • Organizer
      第33回 自己免疫疾患研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 脳梗塞後の炎症の収束と組織修復のメカニズム2018

    • Author(s)
      吉村昭彦、伊藤美菜子
    • Organizer
      第62回サイトカインインターフェロン学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 制御性T細胞のエピジェネティク改変による免疫疾患制御2018

    • Author(s)
      吉村昭彦
    • Organizer
      第25回 日本免疫毒性学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Regulation of Inflammation after Stroke by Macrophages and Regulatory T Cells2018

    • Author(s)
      吉村昭彦、伊藤美菜子
    • Organizer
      Keystone Symposia on New Frontiers in Neuroinflammation,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 脳梗塞における神経症状回復を促す新規免疫細胞の発見

    • URL

      http://kompas.hosp.keio.ac.jp/contents/medical_info/science/201903_02.html

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
  • [Remarks] 脳梗塞慢性期において神経症状を回復させる新規脳内T細胞を発見

    • URL

      https://www.keio.ac.jp/ja/press-releases/2019/1/7/28-50388/

    • Related Report
      2019 Annual Research Report 2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 免疫・炎症性疾患の治療薬2020

    • Inventor(s)
      竹内 勤、吉村昭彦、葛西義明
    • Industrial Property Rights Holder
      竹内 勤、吉村昭彦、葛西義明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] CD45RA+およびCCR7+の細胞表面マーカーを有するT細胞の製造方法(2020

    • Inventor(s)
      吉村昭彦、近藤泰介、富里亘
    • Industrial Property Rights Holder
      吉村昭彦、近藤泰介、富里亘
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report

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Published: 2017-06-01   Modified: 2023-10-16  

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