myeloid derived suppressor cells as a novel immune therapy

• Project/Area Number: 16K09893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kobe University
• Principal Investigator: Morinobu Akio 神戸大学, 医学研究科, 准教授 (10294216)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 関節リウマチ / リウマチ肺 / 樹状細胞 / 骨髄由来抑制細胞 / 骨髄由来抑制性細胞 / 関節炎 / MDSC / 制御性樹状細胞 / 免疫代謝 / アミノ酸 / 骨髄性抑制細胞 / 細胞治療

Outline of Final Research Achievements

In order to　clarify the role for meyloid derived suppressor cells (MDSC) in ILD ion SKG model mice, we examined the function and origin of lung-infiltrating MDSC and MDSC. First we identified MDSC and novel tolerogenic DC-like cells in the inflamed lungs. Next we isolated these populations and co-cultured with T cells to find that both of these cells are immuno-suppressive. The latter cells were induced from total lung cells and lung MDSCs in a TGFb dependent manner.Also adoptive transfer of the latter cells ameriolated the progression of ILD.
Our findings will pave the way to a novel immunosuppressive therapy and cell-based therapies in the future.

Academic Significance and Societal Importance of the Research Achievements

この結果は、炎症部位においては新たな免疫抑制機序が働いていることを示し、新規治療法の開発につながる。
今後はヒトにおいて病勢との関連や、細胞治療への応用のための研究が期待される。

Research Products

• [Journal Article] Myeloid-derived suppressor cells in non-neoplastic inflamed organs (2018)
  • Author(s): Sendo Sho、Saegusa Jun、Morinobu Akio
  • Journal Title: Inflammation and Regeneration Volume: 38 Issue: 1
  • DOI: 10.1186/s41232-018-0076-7
  • NAID: 120006539277
  • Peer Reviewed / Open Access
• [Journal Article] CD11b+ Gr1dim tolerogenic dendritic cell-like cells are expanded in interstitial lung disease in SKG mice. (2017)
  • Author(s): Sendo S, Saegusa J, Okano T, Takahashi S, Akashi K, Morinobu A.
  • Journal Title: Arthritis Rheumatol. Volume: 69 Issue: 12 Pages: 2314-27
  • DOI: 10.1002/art.40231
  • NAID: 120006621623
  • Peer Reviewed
• [Journal Article] Glutaminase 1 plays a key role in the cell growth of fibroblast-like synoviocytes in rheumatoid arthritis. (2017)
  • Author(s): Takahashi S, Saegusa J, Sendo S, Okano T, Akashi K, Irino Y, Morinobu A
  • Journal Title: Arthritis Res Ther. Volume: 19 Issue: 1 Pages: 76-76
  • DOI: 10.1186/s13075-017-1283-3
  • NAID: 120006318800
  • Peer Reviewed / Open Access
• [Journal Article] 3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation. (2017)
  • Author(s): Okano T, Saegusa J, Nishimura K, Takahashi S, Sendo S, Ueda Y, Morinobu A.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 42412-42412
  • DOI: 10.1038/srep42412
  • NAID: 120006624239
  • Peer Reviewed / Open Access
• [Presentation] CD11b+Grldim Tolerogenic Dendritic Cell-Like Cells Suppress the Progression of Interstitial Lung Disease in SKG Mice (2018)
  • Author(s): Sho Sendo, Jun Saegusa, Yoshihide Ichise, Hirotaka Yamada, Ikuko Naka, Yo Ueda, Takaichi Okano, Soshi Takahashi, Akashi Kengo, Akira Onishi, Akio Morinobu*。
  • Organizer: American Colleg of Rheumatology
• [Presentation] Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice. (2018)
  • Author(s): Sendo S*, Saegusa J*, Ichise Y#, Yamada H#, Naka I#, Ueda Y#, Okano T*, Morinobu A*
  • Organizer: American College of Rheumatology 82nd Annual Scientific Meeting.
• [Presentation] CD11b+Grldim Tolerogenic Dendritic Cell-like Cells Differentiated from Monocytic-MDSCs Suppress the Progression of Interstitial Lung Disease in SKG Mice. (2017)
  • Author(s): ２６．Sho Sendo*, Jun Saegusa, Hirotaka Yamada, Yo Ueda, Takaichi Okano, Soshi Takahashi, Akashi Kengo, Akio Morinobu.
  • Organizer: 第46回日本免疫学会学術集会
• [Presentation] Inhibition of the mTOR Pathway and Glutaminolysis Facilitates the Expansion of Myeloid-Derived Suppressor Cells and Synergistically Ameliorates Arthritis in SKG Mice. (2017)
  • Author(s): ２５．Yo Ueda*, Jun Saegusa, Takaichi Okano, Sho Sendo, Keisuke Nishimura, Hirotaka Yamada, Soshi Takahashi, Kengo Akashi, Akio Morinobu.
  • Organizer: 日本免疫学会
• [Presentation] 代謝制御剤による膠原病治療の可能性 (2017)
  • Author(s): 森信 暁雄
  • Organizer: 第45回日本臨床免疫学会総会
  • Invited
• [Presentation] CD11b+Grldim Tolerogenic Dendritic Cell-Like Cells Suppress the Progression of Interstitial Lung Disease in SKG Mice. (2017)
  • Author(s): ２４．Sho Sendo, Jun Saegusa, Yoshihide Ichise, Hirotaka Yamada, Ikuko Naka, Yo Ueda, Takaichi Okano, Soshi Takahashi, Akashi Kengo, Akira Onishi, Akio Morinobu
  • Organizer: American Colleg of Rheumatology
  • Int'l Joint Research
• [Presentation] CD11b+Gr1dim cells, Which Are Induced By GM-CSF Produced By Th17 and Group3 Innate Lymphoid Cell, May Facilitate the Progression of Pneumonitis in SKG Mice (2016)
  • Author(s): Sho Sendo*, Jun Saegusa, Yo Ueda*, Takaichi Okano*, Soshi Takahashi*, Kengo Akashi* and Akio Morinobu*
  • Organizer: 第45回日本免疫学会学術集会
  • Place of Presentation: 沖縄
  • Year and Date: 2016-12-06