NR4A2-mediated regulation of IL-17-producing T cells for novel therapeutic strategy of autoimmune diseases

• Project/Area Number: 21590087
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: OKI Shinji 独立行政法人国立精神・神経医療研究センター, 神経研究所疾病研究第六部, 第三研究室長 (50260328)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 自己免疫疾患 / 核内受容体 / Th17細胞 / 多発性硬化症 / NR4A2 / インターロイキン17 / バイオマーカー

Research Abstract

We identified the orphan nuclear receptor NR4A2 as a most significantly upregulated gene in peripheral T cells obtained from MS patients by microarray analysis. Further analysis employing experimental autoimmune encepharomyelitis(EAE) revealed that NR4A2 expression is selectively associated with IL-17-producing pathogenic T cells and preventive intervention for NR4A2 function ameliorates EAE symptom.

Research Products

• [Journal Article] 多発性硬化症における病原性T細胞のサイトカイン産生制御機構 (2010)
  • Author(s): 大木伸司
  • Journal Title: 生化学(日本生化学会編) Volume: 82 Pages: 745-750
  • NAID: 130006948538
• [Journal Article] 多発性硬化症の自己免疫病態と新規治療戦略 (2010)
  • Author(s): 大木伸司
  • Journal Title: ファルマシア(日本薬学会編) Volume: 46 Pages: 745-749
• [Journal Article] Ustekinumabの有効性と疾患Frontiers in (2010)
  • Author(s): 吉村元、大木伸司
  • Journal Title: Rheumatology & Clinical Immunology Volume: 4 Pages: 57-60
• [Journal Article] Ustekinumabの有効性と疾患 (2010)
  • Author(s): 吉村元、大木伸司
  • Journal Title: Frontiers in Rheumatology & Clinical Immunology Volume: 4 Pages: 57-60
• [Journal Article] Synthetic retinoid AM80 inhibits Th17 cells and ameliorates EAE Am (2009)
  • Author(s): Klemann C, Raveney BJE, Klemann AK, Ozawa T, von Horsten S, Shudo K, Oki S, Yamamura T
  • Journal Title: J. Pathol Volume: 174 Pages: 2234-45
  • URL: http://www.sciencedirect.com/science/article/pii/S0002944010610826
  • Peer Reviewed
• [Journal Article] Synthetic retinoid AM80 inhibits Th17 cells and ameliorates EAE (2009)
  • Author(s): Klemann C.
  • Journal Title: Am.J.Pathol. 174 Pages: 2234-2245
  • Peer Reviewed
• [Journal Article] Suppression of experimental autoimmune encephalomyelitis by ghrelin (2009)
  • Author(s): Theil MM
  • Journal Title: J.Immunol. 181 Pages: 2859-2866
  • Peer Reviewed
• [Journal Article] Versatile orphan nuclear receptor NR4A2 as a promising molecular target for multiple sclerosis and other autoimmune diseases
  • Author(s): Oki S, Raveney BJE, Doi Y, Yamamura T
  • Journal Title: Uehara Memorial Foundation Proceedings ; Chembiomolecular Science : at the Frontier of Chemistry and Biology Volume: (印刷中)
• [Journal Article] Versatile orphan nuclear receptor NR4A2 as a promising molecular target for multiple sclerosis and other autoimmune diseases
  • Author(s): Oki S, Raveney BJE, Doi Y, Yamamura T
  • Journal Title: Uehara Memorial Foundation Proceedings ; Chembiomolecular Science : at the Frontier of Chemistry and Biology Volume: 2,012(印刷中)
• [Presentation] NR4A2 controls Th17-mediated autoimmunity Keystone Symposia 2011 (2012)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: Th17 Cells in Health and Disease(Q2)
  • Place of Presentation: Keystone USA
  • Year and Date: 2012-02-05
• [Presentation] NR4A2 controls Th17-mediated autoimmunity (2012)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: Keystone Symposia 2011 : Th17 Cells in Health and Disease (Q2)
  • Place of Presentation: 米国・キーストーンKeystone Resort Conference Center
  • Year and Date: 2012-02-05
• [Presentation] NR4A2, a nuclear receptor that controls pathogenic Th17 responses during autoimmune disease, is induced in T cells by target organ antigen presenting cells (2011)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: British Society of Immunology Congress
  • Place of Presentation: Liverpool UK
  • Year and Date: 2011-12-05
• [Presentation] NR4A2, a nuclear receptor that controls pathogenic Th17 responses during autoiommune disease, is induced in T cells by target organ antigen presenting cells (2011)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: British Society of Immunology Congress 2011
  • Place of Presentation: 英国・リバプールArena and Convention Center
  • Year and Date: 2011-12-05
• [Presentation] NR4A2, a nuclear receptor that controls pathogenic Th17 responses during autoimmune disease, is induced in T cells by target organ antigen presenting cells (2011)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] NR4A2, a nuclear receptor that controls pathogenic Th17 responses during autoimmune disease is induced in T cells by target organ antigen presenting cells (2011)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-27
• [Presentation] T細胞のInterleukin-9産生に対するレチノイドの制御作用 (2011)
  • Author(s): 野口真行、大木伸司、山村隆
  • Organizer: 第22回日本レチノイド研究会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-11
• [Presentation] T細胞のInterleukin-9産生に対するレチノイドの制御作用 (2011)
  • Author(s): 野口真行、大木伸司、山村隆
  • Organizer: 第22回日本レチノイド研究会
  • Place of Presentation: 日本大学会館(東京都)
  • Year and Date: 2011-11-11
• [Presentation] Th17細胞依存性自己免疫応答に対するオーファン核内受容体NR4A2の機能的連関 (2011)
  • Author(s): 大木伸司、ベン・レイバニー、山村隆
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-31
• [Presentation] Th17細胞依存性自己免疫応答に対するオーファン核内受容体NR4A2の機能的連関 (2011)
  • Author(s): 大木伸司、ベンジャミン・レイバニー、山村隆
  • Organizer: 日本薬学会第131会年会
  • Place of Presentation: 静岡(静岡県コンベンションアーツセンター「グランシップ」、静岡県立大学大講堂、ツインメッセ静岡)
  • Year and Date: 2011-03-28
• [Presentation] 多発性硬化症とサイトカインネットワーク (2010)
  • Author(s): 大木伸司
  • Organizer: 第7回多発性硬化症フォーラム
  • Place of Presentation: 東京(六本木アカデミーヒルズ49)
  • Year and Date: 2010-12-12
• [Presentation] AM80, a synthetic retinoid, ameliorates Th17-mediated autoimmunity of the eye and central nervous system (2010)
  • Author(s): Oki S, Raveney BJE, Klemann C, Yamamura T
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-22
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2010)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-22
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells. (2010)
  • Author(s): Raveney B., S.Oki, T.Yamamura
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸ポートピアホテル、神戸国際展示場)
  • Year and Date: 2010-08-22
• [Presentation] AM80, a synthetic retinoid, ameliorates Th17-mediated autoimmunity of the eye and central nervous system (2010)
  • Author(s): S.Oki, Raveney B., Klemann C., T.Yamamura
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸(神戸ポートピアホテル、神戸国際展示場)
  • Year and Date: 2010-08-22
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2010)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 97h Annual Meeting of the American Association of Immunologist
  • Place of Presentation: Baltimore USA
  • Year and Date: 2010-05-07
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells. (2010)
  • Author(s): Raveney B., S.Oki., T.Yamamura
  • Organizer: 97h Annual Meeting of the American Association of Immunologist
  • Place of Presentation: Baltimore(Baltimore Convention Center), USA
  • Year and Date: 2010-05-07
• [Presentation] 合成レチノイドAm80はTh17依存性眼炎症を抑制しFoxp3陽性T細胞を誘導する (2010)
  • Author(s): 小口翔、ベン・レイバニー、大木伸司、天竺桂弘子、佐藤準一、山村隆
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] 合成レチノイドAm80はTh17依存性眼炎症を抑制しFoxp3陽性T細胞を誘導する (2010)
  • Author(s): 小口翔
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山、岡山コンベンションセンター
  • Year and Date: 2010-03-28
• [Presentation] オーファン核内受容体NR4A2はIL-17産生性T細胞と自己免疫応答に強く連関する (2010)
  • Author(s): 大木伸司、ベン・レイバニー、山村隆
  • Organizer: 第22回日本神経免疫学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-03-17
• [Presentation] オーファン核内受容体NR4A2は1L-17産生性T細胞と自己免疫応答に強く連関する (2010)
  • Author(s): 大木伸司
  • Organizer: 第22回日本神経免疫学会学術集会
  • Place of Presentation: 東京、日経ホール
  • Year and Date: 2010-03-17
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2009)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] AM80, a synthetic retinoid, ameliorates Th17-mediated ocular autoimmunity and promotes the infiltration of Foxp3+T cells into the eye (2009)
  • Author(s): 大木伸司、ベン・レイバニー、山村隆
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] AM80, a synthetic retinoid, ameliorates Th17-mediated ocular autoimmunity and promotes the infiltration of Foxp3+ T cells into the eye (2009)
  • Author(s): 大木伸司
  • Organizer: 第39回 日本免疫学会総会・学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2009)
  • Author(s): Raveney B.J.E.
  • Organizer: 第39回 日本免疫学会総会・学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] T細胞アナジーに関連したE3リガーゼGRAILの基質同定 (2009)
  • Author(s): 市川大樹
  • Organizer: 第39回 日本免疫学会総会・学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2009)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 2nd European Congress of Immunology
  • Place of Presentation: Berlin Germany
  • Year and Date: 2009-09-13
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2009)
  • Author(s): Raveney B.J.E.
  • Organizer: 2nd European Congress of Immunology
  • Place of Presentation: Berlin Germany, International Congress Center
  • Year and Date: 2009-09-13
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2009)
  • Author(s): Raveney BJE, Oki S, Yamamura T
  • Organizer: 9th Annual Conference of FOCIS
  • Place of Presentation: San Fransisco USA
  • Year and Date: 2009-06-11
• [Presentation] Expression of the orphan nuclear receptor NR4A2 is required for IL-17 production by Th17 cells (2009)
  • Author(s): Raveney B.J.E.
  • Organizer: 9th Annual Conference of FOCIS
  • Place of Presentation: San Francisco, USA Marriott Hotel
  • Year and Date: 2009-06-11
• [Presentation] Nuclear receptors as therapeutic targets for multiple sclerosis (2009)
  • Author(s): Oki S
  • Organizer: 2nd Conference of Germany and Japan Neuroimmunology
  • Place of Presentation: Eibsee Germany
  • Year and Date: 2009-06-07
• [Presentation] Nuclear receptors as therapeutic targets for multiple sclerosis (2009)
  • Author(s): Oki S.
  • Organizer: 2nd Conference of Germany and Japan Neuroimmunology
  • Place of Presentation: Eibsee Germany, Eibsee Hotel
  • Year and Date: 2009-06-07
• [Patent(Industrial Property Rights)] IL-17に起因する炎症を改善するための医薬組成物 (2008)
  • Inventor(s): 大木伸司、北條浩彦、三宅幸子、山村隆
  • Industrial Property Rights Holder: 大木伸司、北條浩彦、三宅幸子、山村隆
  • Industrial Property Number: 2009-501299
  • Filing Date: 2008-02-28
• [Patent(Industrial Property Rights)] IL-17産生抑制物質及びそのスクリーニング方法 (2007)
  • Inventor(s): 大木伸司、北條浩彦、三宅幸子、山村隆
  • Industrial Property Rights Holder: 大木伸司、北條浩彦、三宅幸子、山村隆
  • Industrial Property Number: 2007-049768
  • Filing Date: 2007-02-28