Roles of CD300a in the pathogenesis of systemic sclerosis

• Project/Area Number: 16K19603
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kyushu University
• Principal Investigator: Ayano Masahiro 九州大学, 医学研究院, 助教 (40773677)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: CD300a / アポトーシス / ホスファチジルセリン / 全身性強皮症 / CD8陽性T細胞 / 強皮症 / CD8 / T細胞 / エフェクター細胞 / 膠原病学 / 免疫学

Outline of Final Research Achievements

CD300a is identified as a phosphatidylserine receptor and involved in the regulation of apoptosis. In this study, we revealed that CD300a expression on CD8+ T cells was upregulated after activation of the cells, and that CD300a+CD8+ T cells had increased effector functions such as cytokine production and cytotoxic activity. The effector functions were suppressed by the interaction with CD300a and apoptotic cells. CD300a+CD8+ T cells were increased in patients with systemic sclerosis (SSc) compared with healthy controls and were appreciably associated with the severity of skin sclerosis. These findings indicate that upregulated CD300a expression on CD8+ T cells reflects disease severity and is involved in SSc pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

全身性強皮症は既存の免疫抑制療法や分子標的療法では生命予後の改善に乏しく、病態の解明および新規治療法の開発が必要な疾患である。本研究ではCD300a陽性CD8陽性T細胞の機能的特徴を解明し、CD8陽性T細胞がアポトーシス細胞との相互作用を介して機能制御されていることを示した。本研究の結果からCD300aが全身性強皮症の病態に関連することが示唆され、CD300aを標的とした治療法の有効性が期待される。

Research Products

• [Journal Article] CD34-selected versus unmanipulated autologous hematopoietic stem cell transplantation in the treatment of severe systemic sclerosis: a post hoc analysis of a phase I/II clinical trial conducted in Japan. (2019)
  • Author(s): Ayano M, Tsukamoto H, Mitoma H, Kimoto Y, Akahoshi M, Arinobu Y, Miyamoto T, Horiuchi T, Niiro H, Nagafuji K, Harada M, Akashi K
  • Journal Title: Arthritis Res Ther. Volume: 21 Issue: 1 Pages: 30-30
  • DOI: 10.1186/s13075-019-1823-0
  • Peer Reviewed / Open Access
• [Journal Article] Long-term efficacy of infliximab treatment and the predictors of treatment outcomes in patients with refractory uveitis associated with Behcet’s disease. (2018)
  • Author(s): (1)Ueda S, Akahoshi M, Takeda A, Inoue Y, Omoto A, Ayano M, Kimoto Y, Mitoma H, Arinobu Y, Niiro H, Tsukamoto H, Horiuchi T, Hikita SI, Fukuhara T, Ishibashi T, Sonoda KH, Akashi K
  • Journal Title: Eur J Rheumatol Volume: 5 Issue: 1 Pages: 9-15
  • DOI: 10.5152/eurjrheum.2017.17068
  • Peer Reviewed / Open Access
• [Journal Article] Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study (2018)
  • Author(s): (2)Otsuka Y, Kiyohara C, Kashiwado Y, Sawabe T, Nagano S, Kimoto Y, Ayano M, Mitoma H, Akahoshi M, Arinobu Y, Niiro H, Akashi K, Horiuchi T
  • Journal Title: PLoS One Volume: 13 Issue: 4 Pages: e0196368-e0196368
  • DOI: 10.1371/journal.pone.0196368
  • Peer Reviewed / Open Access
• [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 (2018)
  • 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56回九州リウマチ学会
• [Presentation] 全身性エリテマトーデス患者の長期予後に関する検討 (2018)
  • Author(s): 綾野雅宏、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56回九州リウマチ学会
• [Presentation] ループス腎炎に対するタクロリムスの長期使用成績：10年間の検討 (2018)
  • Author(s): 綾野雅宏、中野未来、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62回日本リウマチ学会総会・学術集会