Molecular analysis of pathogenesis on rheumatoid arthritis caused by chemokines CCL19 and CCL21

• Project/Area Number: 22790945
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Toho University
• Principal Investigator: KUWABARA Taku 東邦大学, 医学部, 助教 (40385563)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 臨床免疫学 / 自己免疫疾患 / インターロイキン23 / Th17細胞 / ケモカインCCL19とCCL21 / 樹状細胞 / 関節リウマチ

Research Abstract

The roles for chemokines CCL19 and CCL21 in induction of collagen-induced arthritis (CIA) were investigated plt mutant mice, that lacking expression of CCL19 and CCL21. We found that these mutant mice failed to express inflammatory cytokines and showed resistant to the induction of CIA. Collagen-immunized plt mice decreased IL-23 production in dendritic cells and a concomitant defect in Th17 cells. CCL19- and CCL21-mediated activation of the PI3K/Akt pathway and NF-κB is essential for IL-23 production in dendritic cells. These mechanisms would contribute to the development of strategies to control rheumatoid arthritis.

Research Products

• [Journal Article] CR7 ligands up-regulate IL-23 through PI3-kinase and NF-κB pathway in dendritic cells. (2012)
  • Author(s): Taku Kuwabara, Yuriko Tanaka, Fumio Ishikawa, Motonari Kondo, Hideki Sekiya, and Terutaka Kakiuchi.
  • Journal Title: J. Leuko., Biol. Volume: 92 Pages: 309-318
  • Peer Reviewed
• [Journal Article] Pathogenesis of lupus -like nephritis through autoimmune antibody produced by CD180-negative B lymphocytes in NZBWF1 mouse. (2012)
  • Author(s): Kazuko Fujita, Yoshikiyo Akasaka, Taku Kuwabara, Bing Wang, Kaoru Tanaka, Itaru Kamata, Tomoko Yokoo, Toshio Kinoshita, Ami Iuchi, Yuri Akishima-Fukasawa, Yukio Ishikawa, Motonari Kondo, and Toshiharu Ishii
  • Journal Title: Immunology Letters Volume: 144 Pages: 1-6
  • Peer Reviewed
• [Journal Article] CCR7 ligands up-regulate IL-23 through PI3-kinase and NF-kappaB pathway in dendritic cells (2012)
  • Author(s): Taku Kuwabara
  • Journal Title: Journal of Leukocyte Biology Volume: 92 Pages: 309-318
  • Peer Reviewed
• [Journal Article] Pathogenesis of lupus-like nephritis through autoimmune antibody produced by CD180-negative B lymphocytes in NZBWF1 mouse (2012)
  • Author(s): Fujita K, Akasaka Y, Ishii T
  • Journal Title: Immunol Lett Volume: 144巻 Issue: 1-2 Pages: 1-6
  • DOI: 10.1016/j.imlet.2012.02.012
  • Peer Reviewed
• [Journal Article] Altered antibody production and helper T cell function in mice kacking chemokines CCL19 and CCL21-ser. (2010)
  • Author(s): Kentaro Aritomi, Taku Kuwabara, Yuriko Tanaka, Hideki Nakano, Takuwa Yasuda, Fumio Ishikawa, Hisashi Kurosawa, and Terutaka Kakiuchi
  • Journal Title: Microbiology and Immunology Volume: 54 Issue: 11 Pages: 691-701
  • DOI: 10.1111/j.1348-0421.2010.00266.x
  • Peer Reviewed
• [Journal Article] Altered antibody production and helper T cell function in mice lacking chemokines CCL19 and CCL21-ser (2010)
  • Author(s): Kentaro Aritomi, Taku Kuwabara, et al.
  • Journal Title: Microbiology and immunology Volume: 54 Pages: 691-701
  • NAID: 40017367515
  • Peer Reviewed
• [Presentation] Acetylation modulates interleukin-2 receptor signaling. (2012)
  • Author(s): Taku Kuwabara, and Motonari Kondo
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・福岡マリンメッセ
  • Year and Date: 2012-12-12
• [Presentation] Analysis in expression of CD180 molecules on spleen cells after radiation-induced apoptosis in vivo. (2012)
  • Author(s): Kazuko Fujita, Taku Kuwabara, Bing Wang, Kaoru Tanaka, Yoshikiyo Akasaka, and Toshiharu Ishii
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2012-12-06
• [Presentation] SATB1 is necessary for establishment of immune tolerance. (2012)
  • Author(s): Yuriko Tanaka, Xianghua Guo, Taku Kuwabara, Takanori Mukozu, Fumio Ishikawa, and Motonari Kondo
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2012-12-05
• [Presentation] 妊娠マウスにおける子宮NK細胞の変化について (2011)
  • Author(s): Akiko Takashima, Fumio Ishikawa, TakuKuwabara, Toshihiko Kinoshita, Terutaka Kakiuchi, and Motonari Kondo
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-29
• [Presentation] ケモカインCCL19とCCL21は樹状細胞からのIL-23産生とそれに続くTh17細胞分化を調節する。 (2011)
  • Author(s): 桑原卓、石川文雄、田中ゆり子、岡田弥生、近藤元就、垣内史堂
  • Organizer: 第22回日本生体防御学会学術集会
  • Place of Presentation: 那覇文化テンブス
  • Year and Date: 2011-07-01
• [Presentation] ケモカインCCL19とCCL21は樹状細胞からのIL-23産生を増大しTh17細胞分化を調節する (2011)
  • Author(s): 桑原卓
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇市ぶんかテンブス館(沖縄県)(招待講演)
  • Year and Date: 2011-07-01
• [Presentation] CCL19、CCL21-ser欠損マウス(pltマウス)ではsoluble抗原に対する免疫応答が誘導される。 (2011)
  • Author(s): 田中ゆり子、桑原卓、石川文雄、岡田弥生、近 藤 元 就、垣 内 史 堂
  • Organizer: 第22回日本生体防御学会学術集会
  • Place of Presentation: 那覇文化テンブス
  • Year and Date: 2011-06-30
• [Presentation] CCR7 ligands up-regulate IL-23 through PI30kinase and NF-κB pathways in dendritic cells. (2010)
  • Author(s): Taku Kuwabara, Fumio Ishikawa, Yuriko Tanaka, and Terutaka Kakiuchi
  • Organizer: 14th International congress of Immunology
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-08-24
• [Presentation] Soluble protein antigen efficiently elicits T cell response without any adjuvant in mutant mice lacking expression of CCL19 and CCL21 (plt mice). (2010)
  • Author(s): Yuriko Tanaka, Taku Kuwabara, Fumio Ishikawa, and Terutaka Kakiuchi
  • Organizer: 14thInternational congress of Immunology
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-08-24
• [Presentation] CCR7 ligands up-regulate IL-23 through PI3-kinase and NF-kappaB pathway in dendritic cells (2010)
  • Author(s): Taku Kuwabara
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-24
• [Presentation] Disappearance of natural killer cells in mouse uterus during early pregnancy. (2010)
  • Author(s): Akiko Takashima, Fumio Ishikawa, TakuKuwabara, Yuriko Tanaka, Toshihiko Kinoshita, and Terutaka Kakiuchi
  • Organizer: 14th International congress of Immunology
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-08-23
• [Presentation] Effects of X-ray irradiation on CD180-negative B cells in SLE-model NZBWF1 mice. (2010)
  • Author(s): Kazuko Fujita, Wang Bing, TakuKuwabara, Kaoru Tanaka, Itaru Kamata, Yoshikiyo Akasaka, and Toshihiro Ishii
  • Organizer: 14th International congress of Immunology
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-08-23
• [Presentation] Acetylation modulates interleukin-2 signaling
  • Author(s): 桑原 卓
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡（福岡県）
• [Book] The role of CCR7-ligan in developing experimental autoimmune encephalomyelitis (2011)
  • Author(s): Taku Kuwabara, Yuriko Tanaka, Fumio Ishikawa, Hideki Nakano, and Terutaka Kakicuhi. InTech
  • Publisher: InTech
• [Book] Experimental Autoimmune encephalomyelitis (2011)
  • Author(s): Taku Kuwabara, et al
  • Total Pages: 161
  • Publisher: Intech