Analysis of Th17 axis in the pathogenesis of human rheumatoid arthritis.

• Project/Area Number: 20791032
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Kyoto University
• Principal Investigator: YOSHITOMI Hiroyuki Kyoto University, 医学研究科, 助教 (50402920)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: アレルギー・喘息 / 免疫学 / ケモカイン / TH17 / 関節リウマチ

Research Abstract

IL-1β vigorously induced the production of CCL20 from FLSs of human RA and the production of CCL20 induced by TNF-α was partially attributed to a trace amount of IL-1β induced by TNF-α. The conditioned medium of IL-1β-stimulated FLSs significantly recruited CCR6+ MNCs in a CCL20 dependent manner. Interestingly, CCL20 enhanced the production of IL-6 coordinately with the stimulation of IL-17 but not with that of IFN-g. These findings imply FLSs stimulated by proinflammatory cytokines recruit CCR6+ MNCs including IL-17-producing-helper T cells into the inflamed joint, leading to the enhancement of the production of CCL20, which chemokine and IL-17 coordinately induce proinflammatory cytokines.

Research Products

• [Journal Article] PGE2 inhibits MMP expression by suppressing MKK4-JNK MAP kinase c-JUN pathway via EP4 in human articular chondrocytes. (2010)
  • Author(s): Nishitani K, Ito H, Hiramitsu T, Tsutsumi R, Tanida S, Kitaori T, Yoshitomi H Kobayashi M, Nakamura T.
  • Journal Title: J Cell Biochem. 109(2) Pages: 425-433
  • Peer Reviewed
• [Journal Article] PGE2 inhibits MMP expression by suppressing MKK4-JNK MAP kinase-c-JUN pathway via EP4 in human articular chondrocytes. (2010)
  • Author(s): Nishitani K, Yoshitomi H, et al.
  • Journal Title: J Cell Biochem 109(2) Pages: 425-433
  • Peer Reviewed
• [Journal Article] CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6(+) mononuclear cells and enhances the production of IL-6. (2009)
  • Author(s): Tanida S, Yoshitomi H Nishitani K, Ishikawa M, Kitaori T, Ito H, Nakamura T.
  • Journal Title: Cytokine 47(2) Pages: 112-118
  • Peer Reviewed
• [Journal Article] Mimori T. Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. (2009)
  • Author(s): Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, Nakamura T, Shimizu M, Kawabata D, Yukawa N, Hashimoto M, Sakaguchi N, Sakaguchi S, Yoshifuji H, Nojima T, Ohmura K, Fujii T
  • Journal Title: Arthritis Rheum. 60(8) Pages: 2294-2303
  • Peer Reviewed
• [Journal Article] Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. (2009)
  • Author(s): Kitaori T, Ito H, Schwarz EM, Tsutsumi R, Yoshitomi H, Oishi S, Nakano M, Fujii N, Nagasawa T, Nakamura T
  • Journal Title: Arthritis Rheum 60(3) Pages: 813-823
  • Peer Reviewed
• [Journal Article] CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6+ mononuclear cells and enhances the production of IL-6. (2009)
  • Author(s): Tanida S, Yoshitomi H, et al.
  • Journal Title: Cytokine 42(2) Pages: 112-118
  • Peer Reviewed
• [Journal Article] Severe erosive arthropathy requiring surgical treatments in systemic lupus erythematosus. (2009)
  • Author(s): Kitaori T, Ito H, Yoshitomi H, et al.
  • Journal Title: Mod Rheumatol. 19(4) Pages: 431-436
  • NAID: 10025113669
  • Peer Reviewed
• [Journal Article] Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. (2009)
  • Author(s): Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, et al.
  • Journal Title: Arthritis Rheum. 60(8) Pages: 2294-2303
  • Peer Reviewed
• [Journal Article] Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model (2009)
  • Author(s): Kitaeri T, Ito H, Schwarz EM, Tsuisumi R, Yoehitomi H, Oishi S,. Nakano M, Fujii N, Nagasawa T, Nakamura T.
  • Journal Title: Arthritis Rheumatism 60 Pages: 813-823
  • Peer Reviewed
• [Journal Article] Arthritis and pneumonitis produced by the same T cell clones from mice with spontaneous autoimmune arthritis. (2008)
  • Author(s): Wakasa-Morimoto C, Toyosaki-Maeda T, Matsutani T, Yoshida R, Nakamura-Kikuoka S, Maeda-Tanimura M, Yoshitomi H, Hirota K, Hashimoto M, Masaki H, Fujii Y, Sakata T, Tsuruta Y, Suzuki R, Sakaguchi N, Sakaguchi S
  • Journal Title: Int Immunol 20(10) Pages: 1331-1342
  • NAID: 10024357361
  • Peer Reviewed
• [Presentation] CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6+ mononuclear cells and enhances the production of IL-6 (2010)
  • Author(s): 谷田司明、吉富啓之, 他
  • Organizer: 第56回ORS
  • Place of Presentation: New Orleans U.S.A
  • Year and Date: 2010-03-06
• [Presentation] CCL20 produced in the cytokine network of rheumatoid arthritis recruits CCR6+ mononuclear cells and enhances the production of IL-6. (2010)
  • Author(s): Shimei Tanida, Hiroyuki Yoshitomi, Kohei Nishitani, Masahiro Ishikawa, Toshiyuki Kitaori, Hiromu Ito, Takashi Nakamura
  • Organizer: 56th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: New Orleans
• [Presentation] Involvement of CCL20/CCR6 axis in the pathogenesis of human and murine autoimmune arthritis. (2009)
  • Author(s): 吉富啓之
  • Organizer: Global COE Retreat 2009
  • Place of Presentation: 淡路島
  • Year and Date: 2009-11-07
• [Presentation] RA診療の基本と薬物療法の初歩の初歩 (2009)
  • Author(s): 吉富啓之
  • Organizer: 京都大学整形外科第5回京整会若手研修会
  • Place of Presentation: 京都
  • Year and Date: 2009-09-06
• [Presentation] 関節リウマチの病態におけるリンパ球の役割 (2009)
  • Author(s): 吉富啓之
  • Organizer: 京都大学整形外科19回リウマチ学会近畿支部学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-09-05
• [Presentation] 関節リウマチの病態におけるリンパ球の役割 (2009)
  • Author(s): 吉富啓之
  • Organizer: 第19回日本リウマチ学会近畿支部学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-09-05
• [Book] 「日本医事新報」別冊(【臨床医学の展望】整形外科学) (2010)
  • Author(s): 吉富啓之、中村孝志
  • Total Pages: 7
  • Publisher: 日本医事新報
• [Book] 臨床医学の展望2009(関節リウマチ, No4426) (2009)
  • Author(s): 吉富啓之
  • Publisher: 日本医事新報
• [Book] 「日本医事新報」特集臨床医学の展望2009 (2009)
  • Author(s): 吉富啓之, 他
  • Total Pages: 136
  • Publisher: 日本医事新報社
• [Remarks]
  • URL: http://www.kuhp.kyoto-u.ac.jp/~seikeigeka/fundamental/nankotsu.html