Search for BAFF signaling inhibitors as novel drugs for the treatment of Sjogren's syndrome.

• Project/Area Number: 22591084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Keio University
• Principal Investigator: YOSHIMOTO Keiko 慶應義塾大学, 医学部, 研究員 (20383292)
• Co-Investigator(Renkei-kenkyūsha): TAKEUCHI Tsutomu 慶應義塾大学, 医学部, 教授 (50179610)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 膠原病学 / サイトカイン / シェーグレン症候群 / BAFF / 細胞シグナル伝達 / 単球 / IL-6 / シグナル伝達 / JAK3 / 阻害剤 / リン酸化 / BAFF受容体

Research Abstract

Aiming at development of new disease-modifying drugs for Sjogren's syndrome (SS), we established an in vitro model for the screening of compounds that inhibit signal transduction triggered by a B cell activating factor, BAFF. This model enabled us to anal

Research Products

• [Journal Article] CD3 ζ defects in systemic lupus erythematosus (2012)
  • Author(s): Takeuchi T
  • Journal Title: Ann Rheum Dis (Suppl) Volume: 71 Pages: i78-i81
  • DOI: 10.1136/annrheumdis-2011-200641
  • Peer Reviewed
• [Journal Article] Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjogren's syndrome (2011)
  • Author(s): Yoshimoto K., Tanaka M., et al
  • Journal Title: Arthritis Research and Therapy Volume: 13(5) Issue: 5
  • DOI: 10.1186/ar3493
  • Peer Reviewed
• [Journal Article] 自己免疫疾患の病態形成におけるmTORの関与について (2011)
  • Author(s): 吉本桂子
  • Journal Title: 月刊リウマチ科 Volume: 46(1) Pages: 67-71
  • URL: http://www.kahyo.com/item/R201107-461
• [Journal Article] Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjogren's syndrome (2011)
  • Author(s): Keiko Yoshimoto, et al
  • Journal Title: Arthritis Research and Therapy Volume: 13(5)
  • Peer Reviewed
• [Presentation] Aberrant expression of BAFF receptor (BR3) in peripheral monocytes of patients with primary Sjogren's syndrome impacts abnormal activation of BAFF signaling through IKK-alpha and IKK-beta (2012)
  • Author(s): Yoshimoto K., et al
  • Organizer: American College of Rheumatology Annual Meeting 2012
  • Place of Presentation: ワシントンDC、米国
  • Year and Date: 2012-11-10
• [Presentation] JAK3 is involved in BAFF-mediated abnormal production of IL-6 by peripheral monocytes of patients with primary Sjogren's syndrome (2012)
  • Author(s): Yoshimoto K., et al.
  • Organizer: Cytokines 2012
  • Place of Presentation: ジュネーブ、スイス
  • Year and Date: 2012-09-12
• [Presentation] シェーグレン症候群患者末単球における BAFF シグナル異常の解析 (2012)
  • Author(s): 吉本桂子
  • Organizer: 第21回日本シェーグレン症候群学会
  • Place of Presentation: 京都
  • Year and Date: 2012-09-07
• [Presentation] BAFF signaling is abnormally regulated through JAK pathways in monocytes with primary Sjogren's syndrome (2012)
  • Author(s): Yoshimoto K., et al
  • Organizer: EULAR 2012
  • Place of Presentation: ベルリン、ドイツ
  • Year and Date: 2012-06-08
• [Presentation] JAK-STAT pathways are involved in the BAFF signaling of peripheral monocytes of patients with primary Sjogren's syndrome (2012)
  • Author(s): Yoshimoto K., et al
  • Organizer: Immunology 2012
  • Place of Presentation: ボストン、米国
  • Year and Date: 2012-05-08
• [Presentation] JAK-STAT pathways may be involved in enhanced production of IL-6 by BAFF in human monocytes (2012)
  • Author(s): 吉本桂子
  • Organizer: 第56回日本リウマチ学会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-21
• [Presentation] JAK-STAT pathways are involved in the BAFF signaling of peripheral monocytes of patients with primary Sjögren’s syndrome. (2012)
  • Author(s): Keiko Yoshimoto
  • Organizer: American Association of Immunologist Annual Meeting 2012
  • Place of Presentation: Boston USA
• [Presentation] BAFF signaling is abnormally regulated through JAK pathways in (2012)
  • Author(s): Keiko Yoshimoto
  • Organizer: EULAR 2012
  • Place of Presentation: Berlin Germany
• [Presentation] JAK-STAT pathways may be involved in enhanced production of IL-6 by BAFF in human monocytes. (2012)
  • Author(s): 吉本 桂子
  • Organizer: 日本リウマチ学会総会学術集会
  • Place of Presentation: 東京
• [Presentation] シェーグレン症候群患者末単球におけるBAFFシグナル異常の解析 (2012)
  • Author(s): 吉本 桂子
  • Organizer: 第21回日本シェーグレン症候群学会
  • Place of Presentation: 京都
  • Invited
• [Presentation] JAK3 is involved in BAFF-mediated abnormal production of IL-6 by peripheral monocytes of patients with primary Sjögren’s syndrome (2012)
  • Author(s): Keiko Yoshimoto
  • Organizer: Cytokines 2012
  • Place of Presentation: Geneva Switzerland
• [Presentation] Aberrant expression of BAFF receptor (BR3) in peripheral monocytes of patients with primary Sjögren’s syndrome impacts abnormal activation of BAFF signaling through IKK-alpha and IKK-beta (2012)
  • Author(s): Keiko Yoshimoto
  • Organizer: American College of Rheumatology Annual Meeting 2012
  • Place of Presentation: Washington DC USA
• [Presentation] Possible involvement of JAK3 pathway in production of IL-6 induced by BAFF in peripheral monocytes of patients with primary Sjogren's syndrome (2011)
  • Author(s): Yoshimoto K., et al
  • Organizer: 第40回日本免疫学会総会学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-29
• [Presentation] Possible involvement of JAK3 pathway in production of IL-6 induced by BAFF in peripheral monocytes of patients with primary Sjogren's syndrome (2011)
  • Author(s): Keiko Yoshimoto
  • Organizer: 第40回日本免疫学会総会学術集会
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-29
• [Presentation] Abnormalities in a JAK-STAT pathway are involved in the aberrant production of IL-6 by BAFF-stimulated peripheral monocytes of patients with primary Sjogren's syndrome (2011)
  • Author(s): Yoshimoto K., et al.
  • Organizer: American College of Rheumatology
  • Place of Presentation: シカゴ、米国
  • Year and Date: 2011-11-08
• [Presentation] Abnormalities in a JAK-STAT pathway are involved in the aberrant production of IL-6 by BAFF-stimulated peripheral monocytes of patients with primary Sjogren's syndrome (2011)
  • Author(s): Keiko Yoshimoto
  • Organizer: American College of Rheumatology 2011
  • Place of Presentation: Chicago McCormick Place (Convention Center)(USA)
  • Year and Date: 2011-11-06
• [Presentation] Possible involvement of JAK3 pathway in production of IL-6 induced by BAFF in human monocytes (2011)
  • Author(s): Yoshimoto K., et al
  • Organizer: 4^<th>East Asian Group of Rheumatology
  • Place of Presentation: 東京
  • Year and Date: 2011-10-15
• [Presentation] Possible involvement of JAK3 pathway in production of IL-6 induced by BAFF in human monocytes (2011)
  • Author(s): Keiko Yoshimoto
  • Organizer: 4^<th> East Asian Group of Rheumatology
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2011-10-15
• [Presentation] REGULATION OF IL-6 PRODUCTION INDUCED BY SOLUBLE BAFF IN MONOCYTES OF PATIENTS WITH PRIMARY SJOGREN'S SYNDROME (2011)
  • Author(s): Keiko Yoshimoto
  • Organizer: 11^<th> International Symposium for Sjogren's syndrome
  • Place of Presentation: Athens Athenaeum intercontinental Hotel(ギリミャ)
  • Year and Date: 2011-09-30
• [Presentation] REGULATION OF IL-6 PRODUCTION INDUCED BY SOLUBLE BAFF IN MONOCYTES OF PATIENTS WITH PRIMARY SJoGREN'S SYNDROME (2011)
  • Author(s): Yoshimoto K., et al
  • Organizer: 11^<th> International Symposium for Sjogren's syndrome
  • Place of Presentation: アテネ、ギリシャ
  • Year and Date: 2011-09-29
• [Presentation] シェーグレン症候群患者末単球からの IL-6 産生と BAFF シグナルの関与 (2011)
  • Author(s): 吉本桂子
  • Organizer: 第20回日本シェーグレン症候群学会
  • Place of Presentation: 金沢
  • Year and Date: 2011-09-10
• [Presentation] シェーグレン症候群患者末単球からのIL-6産生とBAFFシグナルの関与 (2011)
  • Author(s): 吉本桂子
  • Organizer: 第20回日本シェーグレン症候群学会
  • Place of Presentation: ホテル金沢(石川)
  • Year and Date: 2011-09-09
• [Presentation] ヒト単球からのBAFF 誘導型IL-6産生における JAK 経路の関与 (2011)
  • Author(s): 吉本桂子
  • Organizer: 第55回日本リウマチ学会総会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2011-07-20
• [Presentation] ヒト単球からのBAFF誘導型IL-6産生におけるJAK経路の関与 (2011)
  • Author(s): 吉本桂子
  • Organizer: 第55回日本リウマチ学会総会学術集会
  • Place of Presentation: ポートピアホテル(兵庫)
  • Year and Date: 2011-07-18
• [Presentation] A JAK3 pathway may be involved in the production of IL-6 by human monocytes stimulated with BAFF. (2011)
  • Author(s): Yoshimoto K., et al.
  • Organizer: Immunology 2011
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2011-05-15
• [Presentation] A JAK3 pathway may be involved in the production of IL-6 by human monocytes stimulated with BAFF (2011)
  • Author(s): Keiko Yoshimoto
  • Organizer: Immunology 2011
  • Place of Presentation: San Francisco (USA) Moscone Center
  • Year and Date: 2011-05-14
• [Presentation] シェーグレン症候群患者の 末梢単球およびT細胞における BAFF産生異常機構と病態形成への関与 (2010)
  • Author(s): 吉本桂子
  • Organizer: 第19回日本シェーグレン症候群学会
  • Place of Presentation: 舞浜市
  • Year and Date: 2010-09-10
• [Presentation] シェーグレン症候群患者の末梢単球およびT細胞におけるBAFF産生異常機構と病態形成への関与 (2010)
  • Author(s): 吉本桂子
  • Organizer: 第19回日本シェーグレン症候群学会
  • Place of Presentation: 舞浜市
  • Year and Date: 2010-09-10
• [Presentation] ヒト単球からのBAFF 誘導型IL-6産生機構の解明 (2010)
  • Author(s): 吉本桂子
  • Organizer: 第75回日本インターフェロン・サイトカイン学会
  • Place of Presentation: 北九州市
  • Year and Date: 2010-06-26
• [Presentation] ヒト単球からのBAFF誘導型IL-6産生機構の解明 (2010)
  • Author(s): 吉本桂子
  • Organizer: 第75回日本インターフェロン・サイトカイン学会
  • Place of Presentation: 北九州市
  • Year and Date: 2010-06-26
• [Presentation] シェーグレン症候群患者末梢単球における BAFF シグナル異常の解析 (2010)
  • Author(s): 吉本桂子
  • Organizer: シェーグレンセミナー 2010
  • Place of Presentation: 東京
  • Year and Date: 2010-06-05
• [Presentation] シェーグレン症候群患者末梢単球におけるBAFFシグナル異常の解析 (2010)
  • Author(s): 吉本桂子
  • Organizer: シェーグレン症候群セミナー
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2010-05-23
• [Presentation] Up-regulated signaling pathway triggered by sBAFF may induce aberrant production of IL-6 in monocytes of the patients with Sjogren's Syndrome (2010)
  • Author(s): 吉本桂子
  • Organizer: Immunology 2010
  • Place of Presentation: ボルチモア(米国)
  • Year and Date: 2010-05-11
• [Presentation] Up-regulated signaling pathway triggered by sBAFF may induce aberrant production of IL-6 in monocytes of the patients with Sjogren's Syndrome (2010)
  • Author(s): Yoshimoto K., at al.
  • Organizer: Immunology 2010
  • Place of Presentation: ボルチモア, 米国
  • Year and Date: 2010-05-08