Autophagy and Presentation of Citrullinated Antigen in Rheumatoid Arthritis

• Project/Area Number: 16K19591
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Hokkaido University
• Principal Investigator: Kato Masaru 北海道大学, 大学病院, 助教 (10755896)
• Research Collaborator: SUGAWARA Eri 北海道大学, 医学院, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 関節リウマチ / オートファジー / シトルリン化 / 抗原提示 / ビメンチン / 内科 / リウマチ学

Outline of Final Research Achievements

This study has clarified that (1) synovial fibroblasts express MHC class II and costimulatory molecules upon stimulation with IFN-gamma, (2) citrullinated vimentin in synovial fibroblasts is recognized by anti-citrullinated peptide antibodies from rheumatoid arthritis patients, (3) citrullinated vimentin binds to MHC class II, and (4) citrullinated vimentin is increased by the induction of autophagy while is decreased by autophagy inhibition. These results are novel findings in the pathogenesis of rheumatoid arthritis, particularly in its autoimmunity, and suggest a role of synovial fibroblasts in the production of anti-citrullinated peptide antibodies through autophagy.

Research Products

• [Journal Article] The role of genetics and epigenetics in rheumatic diseases: Are they really a target to be aimed at? (2018)
  • Author(s): Kato M, Yasuda S, Atsumi T
  • Journal Title: Rheumatology International Volume: in press Issue: 8 Pages: 1333-1338
  • DOI: 10.1007/s00296-018-4026-0
  • Peer Reviewed
• [Journal Article] AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts (2017)
  • Author(s): Kato M, Ospelt C, Kolling C, Shimizu T, Kono M, Yasuda S, Michel BA, Gay RE, Gay S, Klein K, Atsumi T
  • Journal Title: Oncotarget Volume: 7 Issue: 39 Pages: 64221-32
  • DOI: 10.18632/oncotarget.11890
  • NAID: 120005905626
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Autophagy promotes citrullination of vimentin in synovial fibroblasts (2018)
  • Author(s): Sugawara E, Kato M, Hisada R, Fujieda Y, Oku K, Bohgaki T, Amengual O, Yasuda S, Atsumi T
  • Organizer: The 62nd Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
• [Presentation] Autophagy promotes citrullination of vimentin in synovial fibroblasts (2017)
  • Author(s): Sugawara E, Kato M, Hisada R, Fujieda Y, Oku K, Bohgaki T, Yasuda S, Amengual O, Atsumi T
  • Organizer: The 61st Annual General Assembly and Scientific Meeting of the Japan College of Rheumatology
  • Place of Presentation: 福岡国際会議場（福岡県福岡市）
  • Year and Date: 2017-04-20
• [Presentation] The role of ubiquitin-binding proteins in rheumatoid arthritis synovial fibroblasts (2016)
  • Author(s): Kato M, Atsumi T
  • Organizer: 8th International Forum on Rheumatoid Arthritis
  • Place of Presentation: 品川プリンスホテル（東京都港区）
  • Year and Date: 2016-10-21
  • Int'l Joint Research