Could IL-34, which is involved in inflammation and bone resorption, be a target molecule for the treatment of rheumatoid arthritis?

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08420
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: NAGAFUCHI Hiroko 聖マリアンナ医科大学, 医学部, 講師 (80278001)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: IL-34 / 関節リウマチ

Outline of Final Research Achievements

Regulation of inflammation and bone destruction are important in the treatment of rheumatoid arthritis (RA).The role of Interleukin (IL)-34　is a cytokine involved in chronic inflammation and bone resorption. I investigated the role of IL-34 in the pathogenesis of RA. IL-34 was significantly increased in RA patient serum compared to osteoarthritis (OA) and spontaneously produced IL-34 in the culture supernatant of RA primary synovial cells. RA fibroblast-like synoviocytes (FLS) express CSF-1R, a receptor for IL-34, and produced IL-34 upon IL-1 and TNFα stimulation; RAFLS produced IL-6 upon IL-34 stimulation; IL-6 produced by RAFLS stimulated with IL-1 was suppressed by anti-IL-34 and anti-CSF-1R antibodies The results indicate that IL-34 is involved in the pathogenesis of RA patients.IL-34 is a potential target for RA therapy.

Free Research Field

リウマチ・膠原病学

Academic Significance and Societal Importance of the Research Achievements

IL-34は慢性炎症と骨吸収に関与するサイトカインである一方で、肺がん患者や免疫チェックポイント阻害薬で治療抵抗性の獲得に関与するサイトカインであることが知られている。IL-34は肺がんでの治療標的になることも報告がある。今回研究者は関節リウマチ(RA)患者でIL-34が治療の標的となる可能性を明らかにした。担癌RA患者でのRA治療はガイドラインがなく、また免疫抑制剤は腫瘍免疫の抑制が懸念される。IL-34を標的にしたRA治療の開発は担癌RA患者でも有用である可能性があり、有意義な研究成果であったと考える。