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Roles of CD226 in the pathogenesis of systemic lupus erythematosus

Research Project

Project/Area Number 19K17887
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionKyushu University

Principal Investigator

Masahiro Ayano  九州大学, 医学研究院, 助教 (40773677)

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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsCD226 / 全身性エリテマトーデス / ループス腎炎 / B細胞 / バイオマーカー
Outline of Research at the Start

全身性エリテマトーデス(SLE)の病態には過剰な自己への免疫応答が関与しており、多くの細胞の相互作用に関わる共刺激分子を標的とした治療戦略は有用と考えられる。CD226は近年SLEの新規疾患感受性遺伝子として報告された共刺激分子であり、CD226を標的とする治療はSLEの病態に関与する細胞を多面的に制御できる可能性がある。本研究は、SLEの病態形成におけるCD226の機能を明らかにし、CD226を標的とする治療法を確立することを目的として行う。

Outline of Final Research Achievements

This study aimed to reveal the involvement of CD226 in the pathogenesis of systemic lupus erythematosus (SLE) by assessing the relationship between CD226-expressing B cells or soluble CD226 and the disease activity, clinical manifestations, and prognosis of SLE. We demonstrated that the proportion of CD226+ B cells increased in SLE patients and could be associated with disease activity and prognosis. We also showed that serum soluble CD226 levels were elevated in active SLE patients and were associated with disease activity and flares. Thus, CD226+ B cells and soluble CD226 may be useful biomarkers for SLE, and its monitoring allows for more precise SLE management.

Academic Significance and Societal Importance of the Research Achievements

全身性エリテマトーデス(SLE)は治療薬や治療戦略の進歩に伴い長期予後は改善しつつあるが十分ではなく、依然として腎炎や中枢神経病変など難治性病態が残存している。本研究では、B細胞のCD226陽性率および血清可溶型CD226濃度がSLEの難治性病態および予後を反映しSLE診療における有用なバイオマーカーになり得ることを示した。これらを用いることでSLE診療の質の向上、長期予後の改善につながることが期待される。

Report

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

    (18 results)

All 2022 2021 2020 2019

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 10 results) Presentation (3 results)

  • [Journal Article] TNFR2 Signaling Enhances Suppressive Abilities of Human Circulating T Follicular Regulatory Cells2022

    • Author(s)
      Kawano Shotaro、Mitoma Hiroki、Inokuchi Shoichiro、Yamauchi Yusuke、Yokoyama Kana、Nogami Jumpei、Semba Yuichiro、Ayano Masahiro、Kimoto Yasutaka、Akahoshi Mitsuteru、Ono Nobuyuki、Arinobu Yojiro、Akashi Koichi、Horiuchi Takahiko、Niiro Hiroaki
    • Journal Title

      The Journal of Immunology

      Volume: 208 Issue: 5 Pages: 1057-1065

    • DOI

      10.4049/jimmunol.2100323

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus2021

    • Author(s)
      Nakano Miki、Ayano Masahiro、Kushimoto Kazuo、Kawano Shotaro、Higashioka Kazuhiko、Inokuchi Shoichiro、Mitoma Hiroki、Kimoto Yasutaka、Akahoshi Mitsuteru、Ono Nobuyuki、Arinobu Yojiro、Akashi Koichi、Horiuchi Takahiko、Niiro Hiroaki
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41598-021-95711-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased proportion of CD226+ B Cells is associated with the disease activitiy and prognosis of systemic lupus erythematosus.2021

    • Author(s)
      61.Nakano M, Ayano M, Kushimoto K, Kawano S, Higashioka K, Inokuchi S, Mitoma H, Kimoto Y, Akahoshi M, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Front Immunol

      Volume: 12 Pages: 713225-713225

    • DOI

      10.3389/fimmu.2021.713225

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydroxychloroquine versus tacrolimus for the treatment of persistently active systemic lupus erythematosus2021

    • Author(s)
      Ayano Masahiro、Kimoto Yasutaka、Mitoma Hiroki、Akahoshi Mitsuteru、Ono Nobuyuki、Arinobu Yojiro、Akashi Koichi、Horiuchi Takahiko、Niiro Hiroaki
    • Journal Title

      Modern Rheumatology

      Volume: 32 Issue: 2 Pages: 345-350

    • DOI

      10.1093/mr/roab010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HLA-B52 allele in giant cell arteritis may indicate diffuse large-vessel vasculitis formation: retrospective study.2021

    • Author(s)
      64.Kushimoto K, Ayano M, Nishimura K, Nakano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Arthritis Res Ther

      Volume: 23 Issue: 1 Pages: 238-238

    • DOI

      10.1186/s13075-021-02618-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictive factors of fetal and maternal pregnancy outcomes in Japanese patients with systemic lupus erythematosus.2021

    • Author(s)
      Irino K, Arinobu Y, Ayano M, Kawano S, Kimoto Y, Mitoma H, Akahoshi M, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Lupus

      Volume: 30 Issue: 10 Pages: 1637-1643

    • DOI

      10.1177/09612033211031989

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type 1 helper T cells generate CXCL9/10-producing T-bet + effector B cells potentially involved in the pathogenesis of rheumatoid arthritis2021

    • Author(s)
      Nakayama T, Yoshimura M, Higashioka K, Miyawaki K, Ota Y, Ayano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Kikukawa M, Yamada H, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Cell Immunol.

      Volume: 360 Pages: 104263-104263

    • DOI

      10.1016/j.cellimm.2020.104263

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of caspase-1 is mediated by stimulation of interferon genes and NLR family pyrin domain containing 3 in monocytes of active systemic lupus erythematosus2021

    • Author(s)
      Inokuchi S, Mitoma H, Kawano S, Ayano M, Kimoto Y, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Clin Exp Rheumatol.

      Volume: -

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Human PD-1 hi CD8 + T Cells Are a Cellular Source of IL-21 in Rheumatoid Arthritis2021

    • Author(s)
      Higashioka K, Yoshimura M, Sakuragi T, Ayano M, Kimoto Y, Mitoma H, Ono N, Arinobu Y, Kikukawa M, Yamada H, Horiuchi T, Akashi K, Niiro H.
    • Journal Title

      Front Immunol.

      Volume: 12 Pages: 654623-654623

    • DOI

      10.3389/fimmu.2021.654623

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shoulder ultrasound and serum lactate dehydrogenase predict inadequate response to glucocorticoid treatment in patients with polymyalgia rheumatica.2020

    • Author(s)
      Ayano M, Arinobu Y, Tsukamoto H, Ota SI, Misaki K, Nishimura K, Kimoto Y, Mitoma H, Akahoshi M, Akashi K, Horiuchi T, Niiro H.
    • Journal Title

      Rheumatology International

      Volume: - Issue: 7 Pages: 1101-1109

    • DOI

      10.1007/s00296-020-04512-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homeostatic Milieu Induces Production of Deoxyribonuclease 1-like 3 from Myeloid Cells.2020

    • Author(s)
      Inokuchi S, Mitoma H, Kawano S, et. al.
    • Journal Title

      J Immunol.

      Volume: 204 Issue: 8 Pages: 2088-2097

    • DOI

      10.4049/jimmunol.1901304

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of circulating SLAMF7+Tfh1 cells with IgG4 levels in patients with IgG4-related disease.2020

    • Author(s)
      Higashioka K, Ota Y, Maehara T, et. al.
    • Journal Title

      BMC Immunol.

      Volume: 21 Issue: 1 Pages: 31-31

    • DOI

      10.1186/s12865-020-00361-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of a novel CD30 + B cell subset producing GM-CSF and its possible link to the pathogenesis of systemic sclerosis2020

    • Author(s)
      Higashioka K, Kikushige Y, Ayano M, Kimoto Y, Mitoma H, Kikukawa M, Akahoshi M, Arinobu Y, Horiuchi T, Akashi K, Niiro H.
    • Journal Title

      Clin Exp Immunol.

      Volume: 201 Issue: 3 Pages: 233-243

    • DOI

      10.1111/cei.13477

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Methotrexate Enhances Apoptosis of Transmembrane TNF-Expressing Cells Treated With Anti-TNF Agents2020

    • Author(s)
      Wang Q, Oryoji D, Mitoma H, Kimoto Y, Koyanagi M, Yokoyama K, Ayano M, Akahoshi M, Arinobu Y, Niiro H, Akashi K, Horiuchi T.
    • Journal Title

      Front Immunol.

      Volume: 14 Pages: 2042-2042

    • DOI

      10.3389/fimmu.2020.02042

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCR6+ group 3 innate lymphoid cells accumulate in inflamed joints in rheumatoid arthritis and produce Th17 cytokines2019

    • Author(s)
      Takaki-Kuwahara Ayako、Arinobu Yojiro、Miyawaki Kohta、Yamada Hisakata、Tsuzuki Hirofumi、Irino Kensuke、Ayano Masahiro、Kimoto Yasutaka、Mitoma Hiroki、Akahoshi Mitsuteru、Tsukamoto Hiroshi、Horiuchi Takahiko、Niiro Hiroaki、Akashi Koichi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 21 Issue: 1 Pages: 198-198

    • DOI

      10.1186/s13075-019-1984-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 全身性エリテマトーデスに対するヒドロキシクロロキンのステロイド減量効果:タクロリムスとの比較検討2019

    • Author(s)
      綾野 雅宏、赤星 光輝、木本 泰孝、三苫 弘喜、 有信 洋二郎、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全身性エリテマトーデス患者における血清可溶型CD226濃度の臨床的意義2019

    • Author(s)
      中野 未来、綾野 雅宏、久志本 和郎、河野 正太郎、木本 泰孝、三苫 弘喜、赤星 光輝、有信 洋二郎、赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全身性強皮症に対する自家造血幹細胞移植の長期成績2019

    • Author(s)
      綾野 雅宏、三苫 弘喜、塚本 浩、柏戸 佑介、 木本 泰孝、赤星 光輝、有信 洋二郎、 赤司 浩一、堀内 孝彦、新納 宏昭
    • Organizer
      第63回日本リウマチ学会総会・学術集会
    • Related Report
      2019 Research-status Report

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

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