Role for MDSC in the pathogenesis of autoimmune diseases and its application for therapy

• Project/Area Number: 24659473
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kobe University
• Principal Investigator: MORINOBU Akio 神戸大学, 医学(系)研究科(研究院), 准教授 (10294216)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 関節リウマチ / 抑制性単球 / JAK阻害剤 / 抑制性骨髄細胞 / MDSC / 関節炎

Research Abstract

We have examined the role for MDSC (myeloid derived suppressor cells) in SKG arthritis model mouse. MDSC number was increased in arthritic mice and injection of MDSC reduced arthritis, indicating that MDSC is induced in arthritis and inhibits arthritis. Furthermore, we found that a JAK inhibitor up-regukates MDSCs in arthritis model mouse in vivo, and depletion of MDSC by anti-Gr-1 antibody accelerated arthritis, indicating that JAK inhibitor ameliorates arthritis in part by inducing MDSC. MDSC is deeply involved in arthritis and could be a thrapeutic target.

Research Products

• [Journal Article] GC/MS-based metabolomics detects metabolic alterations in serum from SLE patients (2014)
  • Author(s): Saegusa J, Irino Y, Yoshida M, Tanaka S, Kogata Y, Kageyama G, Tsuji G, Takenawa T, Kawano S, Kumagai S, Morinobu A.
  • Journal Title: Clin Exp Rheumatol Volume: 32(1) Pages: 148-148
  • Peer Reviewed
• [Journal Article] GC/MS-based metabolomics detects metabolic alterations in serum from SLE patients. (2014)
  • Author(s): 1. Saegusa J, Irino Y, Yoshida M, Tanaka S, Kogata Y, Kageyama G, Tsuji G, Takenawa T, Kawano S, Kumagai S, Morinobu A.
  • Journal Title: Clin Exp Rheumatol Volume: 32 Pages: 148-148
  • Peer Reviewed
• [Journal Article] CD45RA-Foxp3high activated/effector regulatory T cells in the CCR7+CD45RA-CD27+CD28+central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis (2013)
  • Author(s): Matsuki F, Saegusa J, Miyamoto Y, Misaki K, Kumagai S, Morinobu A.
  • Journal Title: Biochem Biophys Res Commun Volume: 438(4)(pii : S0006-291X(13)00938-8) Pages: 778-83
  • Peer Reviewed
• [Journal Article] CD45RA-Foxp3high activated/effector regulatory T cells in the CCR7+CD45RA-CD27+CD28+ central memory subset are decreased in peripheral blood from patients with rheumatoid arthritis. (2013)
  • Author(s): 23. Matsuki F, Saegusa J, Miyamoto Y, Misaki K, Kumagai S, Morinobu A
  • Journal Title: Biochem Biophys Res Commun Volume: 438 Issue: 4 Pages: 778-183
  • DOI: 10.1016/j.bbrc.2013.05.120
  • Peer Reviewed
• [Journal Article] Cancer incidence in systemic sclerosis: Meta-analysis of population-based cohort studies. (2013)
  • Author(s): Onishi A, Sugiyama D, Kumagai S, Morinobu A.
  • Journal Title: Arthritis Rheum Volume: [Epub ahead of print Issue: 7 Pages: 1913-1921
  • DOI: 10.1002/art.37969
  • Peer Reviewed
• [Journal Article] Podoplanin is an inflammatory protein upregulated in Th17 cells in SKG arthritic joints. (2013)
  • Author(s): Miyamoto Y, Uga H, Tanaka S, Kadowaki M, Ikeda M, Saegusa J, Morinobu A, Kumagai S, Kurata H.
  • Journal Title: Mol Immunol. Volume: 54 Issue: 2 Pages: 199-207
  • DOI: 10.1016/j.molimm.2012.11.013
  • Peer Reviewed
• [Presentation] TofacitinibはMyeloid-derived suppressor cellを誘導し、SKGマウス関節炎を抑制する (2014)
  • Author(s): 西村啓佑、三枝淳、明石健吾、西田美和、高橋宗史、古形芳則、蔭山豪一、森信暁雄
  • Organizer: 日本リウマチ学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-24
• [Presentation] 5. TofacitinibはMyeloid-derived suppressor cellを誘導し、SKGマウス関節炎を抑制する。 (2014)
  • Author(s): 西村 啓佑、三枝 淳、明石 健吾、西田 美和、高橋 宗史、古形 芳則、蔭山 豪一、森信 暁雄。
  • Organizer: 日本リウマチ学会学術集会
  • Place of Presentation: グランドプリンスホテル高輪
• [Presentation] Tofacitinib fascilitates expansion of myeloid derived suppressor cells and ameliorates arthritis in SKG mice (2013)
  • Author(s): Nishimura K, Saegusa J, Akashi K, Morinobu A.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2013-12-12
• [Presentation] CD45RA-FoxP3 high activated/effector T regulatory cells in the CCR7+CD45RA-CD27+CD28+ central memory subset are decreased in peripheral blood from patients with RA (2013)
  • Author(s): Saegusa J, Kumagai S, Morinobu A.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張
  • Year and Date: 2013-12-12
• [Presentation] TofacitinibはMyeloid-derived suppressor cellを誘導し、マウス関節炎を抑制する (2013)
  • Author(s): 西村啓佑、三枝淳,松木郁親,田中姿乃,明石健吾,森信暁雄
  • Organizer: 日本臨床免疫学会
  • Place of Presentation: 下関
  • Year and Date: 2013-11-27
• [Presentation] 7. Tofacitinib fascilitates expansion of myeloid derived suppressor cells and ameliorates arthritis in SKG mice. (2013)
  • Author(s): Nishimura K, Saegusa J, Akashi K, Morinobu A.
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
• [Presentation] 10. TofacitinibはMyeloid-derived suppressor cellを誘導し、マウス関節炎を抑制する。 (2013)
  • Author(s): 西村 啓佑、三枝 淳, 松木 郁親, 田中 姿乃, 明石 健吾, 森信 暁雄。
  • Organizer: 日本臨床免疫学会
  • Place of Presentation: 海峡メッセ下関
• [Presentation] 関節リウマチの病態に関与するCD4陽性T細胞サブセットの同定 (2012)
  • Author(s): 松木 郁親, 三枝 淳, 熊谷 俊一, 森信 暁雄
  • Organizer: 日本臨床免疫学会
  • Place of Presentation: 東京 京王プラザホテル
• [Presentation] Th17細胞はSKG関節炎モデルマウスの病態形成に関与する (2012)
  • Author(s): 宮本 佳昭, 池田 昌郁, 宇賀 均, 三枝 淳, 森信 暁雄, 熊谷 俊一, 倉田 寛一
  • Organizer: 日本臨床免疫学会
  • Place of Presentation: 東京 京王プラザホテル