Establishment of novel strategy to treat rheumatoid arthritis by regulating intracellular zinc

• Project/Area Number: 15K09521
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Chiba University
• Principal Investigator: Ikeda Kei 千葉大学, 医学部附属病院, 講師 (10456014)
• Co-Investigator(Kenkyū-buntansha): 中島 裕史 千葉大学, 大学院医学研究院, 教授 (00322024) ; 須藤 明 千葉大学, 大学院医学研究院, 准教授 (50447306)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 関節炎 / 亜鉛 / 軟骨 / ヘルパーT細胞 / 関節リウマチ

Outline of Final Research Achievements

mRNA expressions of MTF-1 and MMP-3 were increased in the cartilage of ankle in mouse arthritis model (CIA). However, CIA did not exacerbate in cartilage-specific ZIP8 transgenic mice or cartilage-specific MT-1/2 knockout mice. On the other hand, no correlations were identified between mRNA expression of zinc transporters and intracellular zinc concentration in Th17 cells differentiated from mouse naive helper T cells. Furthermore, MT-1/2 knockdown did not affect helper T cell differentiation in vitro.
These data indicate that zinc transporters are not likely to play significant roles in arthritis or helper T cell differentiation in mice.

Research Products

• [Journal Article] Helios enhances regulatory T cell function in cooperation with Foxp3 (2015)
  • Author(s): Takatori H, Kawashima H, Matsuki A, Meguro K, Tanaka S, Iwamoto T, Sanayama Y, Nishikawa N, Tamachi T, Ikeda K, Suto A, Suzuki K, Kagami S, Hirose K, Kubo M, Hori S, Nakajima H
  • Journal Title: Arthritis Rheumatol Volume: 67 Issue: 6 Pages: 1491-502
  • DOI: 10.1002/art.39091
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of B Cell Leukemia/Lymphoma 3 in the development of T follicular helper cells and the pathogenesis of rheumatoid arthritis. (2015)
  • Author(s): Meguro, K., Suzuki, K., Hosokawa, J., Sanayama, Y., Tanaka, S., Furuta, S., Ikeda, K., Takatori, H, Suto, A., Sakamoto, A., Ohara, O., Nakajima, H.
  • Journal Title: Arthritis & Rheumatology Volume: 67 Issue: 10 Pages: 2651-60
  • DOI: 10.1002/art.39266
  • Peer Reviewed / Int'l Joint Research