Development of therapy for rheumatoid arthritis to correct the dysfunction of dendritic cells caused by human parvovirus B19

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790957
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Infectious disease medicine
• Research Institution: Keio University
• Principal Investigator: TAKAHASHI Reiko Keio University, 医学部, 助教 (90422120)
• Project Period (FY): 2009 – 2010
• Keywords: ウイルス / 臨床免疫学 / サイトカイン / 抑制性T細胞

Research Abstract

In this study, we have the purpose to clarify the associations between the pathogenesis of autoimmunity and the dysregulation of cytokine signaling, because we experienced patients infected by human parvovirus B19 followed by onset of rheumatoid arthritis. Regulatory T cells (Tregs) are main cell subset to have suppressive immunological functions. However, the development or maintenance of Tregs has not been clarified to be associated with the dysregulation of cytokine signaling. Therefore, we examined the role of SOCS1, which is the negative regulation of the cytokine-JAK-STAT pathway, in Tregs. We clarified SOCS1 is necessary for Treg function to suppress cytokine signaling and Foxp3 maintenance.

Research Products

• [Journal Article] Suppressors of Cytokine Signaling (SOCS) Proteins and JAK/STAT Pathways : Regulation of T-Cell Inflammation by SOCS1 and SOCS3. (2011)
  • Author(s): Tamiya T, Kashiwagi I, Takahashi R, Yasukawa H, Yoshimura A.
  • Journal Title: Arterioscler Thromb Vasc Biol. 31 Pages: 980-985
  • Peer Reviewed
• [Journal Article] SOCS1 regulates type I/type II NKT cell balance by regulating IFNgamma signaling. (2011)
  • Author(s): Hashimoto M, Hiwatashi K, Ichiyama K, Morita R, Sekiya T, Kimura A, Sugiyama Y, Sibata T, Kuroda K, Takahashi R, Yoshimura A.
  • Journal Title: Int Immunol. 23 Pages: 165-176
  • Peer Reviewed
• [Journal Article] Smad2 and Smad3 are redundantly essential for the TGF -beta-mediated regulation of regulatory T plasticity and Th1 development. (2010)
  • Author(s): Takimoto T, Wakabayashi Y, Sekiya T, Inoue N, Morita R, Ichiyama K, Takahashi R, Asakawa M, Muto G, Mori T, Hasegawa E, Saika S, Hara T, Nomura M, Yoshimura A.
  • Journal Title: J Immunol 185 Pages: 842-855
  • Peer Reviewed
• [Journal Article] Transcription Factor Smad-Independent T Helper 17 Cell Induction by Transforming-Growth Factor-β Is Mediated by Suppression of Eomesodermin
  • Author(s): Ichiyama K, Sekiya T, Inoue N, Tamiya T, Kashiwagi I, Kimura A, Morita R, Muto G, Shichita T, Takahashi R, Yoshimura A
  • Journal Title: Immunity (in press)
  • Peer Reviewed
• [Presentation] SOCS1 Mediates Stabilization of Foxp3 Expression in Treg Cells Keystone symposia (2010)
  • Author(s): 高橋令子, 吉村昭彦
  • Place of Presentation: Taos, USA
  • Year and Date: 20100221-20100226
• [Presentation] SOCS1 is necessary for stable expression of Foxp3 and suppression of IFN-gamma production in nTreg (2010)
  • Author(s): 高橋令子, 吉村昭彦
  • Organizer: 第14回国際免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-22
• [Presentation] SOCS1 mediates stabilization of Foxp3 expression in regulatory T cells (2009)
  • Author(s): 高橋令子, 中川竜介, 吉村昭彦
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] 制御性T細胞におけるFoxp3発現の安定性へのSOCS1の関与 (2009)
  • Author(s): 高橋令子, 中川竜介, 吉村昭彦
  • Organizer: 第37回日本臨床免疫学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-11-14
• [Remarks] ホームページ等 なし