Physiological roles of signal transducers and modulators in the regulation of B cell functions.

• Project/Area Number: 20590492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Keio University
• Principal Investigator: KOBAYASHI Takashi Keio University, 医学部, 准教授 (30380520)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: シグナル伝達 / B細胞 / 抗体 / アレルギー / 抗体産生 / 細胞分化 / サイトカイン / SOCS / TRAF6

Research Abstract

Physiological roles of signal transducers and modulators in B cells were investigated. It has been clarified that TRAF6, a signal transducer of CD40 and Toll-like receptor family, is necessary for an appropriate humoral immune response and the development of a certain B cell subset. On the other hand, SOCS1, a suppressor of cytokine signaling, regulates the susceptibility to IgE-dependent allergic responses in vivo by suppressing IL-4/STAT6 pathway and subsequent IgE production in B cells.

Research Products

• [Journal Article] Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations. (2011)
  • Author(s): Nakaya M, Hamano S, Kawasumi M, Yoshida H, Yoshimura A, Kobayashi T
  • Journal Title: Int Immunol. 23 Pages: 195-202
  • Peer Reviewed
• [Journal Article] Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations. (2011)
  • Author(s): Nakaya M, et al.
  • Journal Title: Int Immunol. Volume: 23 Pages: 195-202
  • Peer Reviewed
• [Journal Article] 自己免疫疾患と炎症 (2010)
  • Author(s): 永淵正法, ほか
  • Journal Title: 細胞工学 Volume: 29 Pages: 769-776
• [Journal Article] TRAF6 is required for generation of the B-1a B cell compartment as well as T cell-dependent and -independent humoral immune responses. (2009)
  • Author(s): Kobayashi T, Kim TS, Jacob A, Walsh MC, Kadono Y, Fuentes-Panana E, Yoshioka T, Yoshimura A, Yamamoto M, Kaisho T, Akira S, Monroe JG, Choi Y
  • Journal Title: PLoS ONE. 4(3)
  • Peer Reviewed
• [Journal Article] Cyclic adenosine monophosphate suppresses the transcription of proinflammatory cytokines via the phosphorylated c-Fos protein. (2009)
  • Author(s): Koga K, Takaesu G, Yoshida R, Nakaya M, Kobayashi T, Kinjyo I, Yoshimura A
  • Journal Title: Immunity 30(3) Pages: 372-383
  • Peer Reviewed
• [Journal Article] TRAF6 is required for generation of the B-la B cell compartment as well as T cell-dependent and -independent humoral immune responses. (2009)
  • Author(s): Kobayashi T., et al.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] TRAF6 and MEKK1 Play a Pivotal Role in the RIG-I-like Helicase Antiviral Pathway. (2008)
  • Author(s): Yoshida R, Takaesu G, Yoshida H, Okamoto F, Yoshioka T, Choi Y, Akira S, Kawai T, Yoshimura A, Kobayashi T
  • Journal Title: J Biol Chem. 283(52) Pages: 36211-36220
  • Peer Reviewed
• [Journal Article] FLN29 deficiency reveals its negative regulatory role in the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway. (2008)
  • Author(s): Sanada T, Takaesu G, Mashima R, Yoshida R, Kobayashi T, Yoshimura A
  • Journal Title: J Biol Chem. 283(49) Pages: 33858-33864
  • Peer Reviewed
• [Journal Article] Foxp3 inhibits RORgamma t-mediated IL-17A mRNA transcription through direct interaction with RORgamma t. (2008)
  • Author(s): Ichiyama K, Yoshida H, Wakabayashi Y, Chinen T, Saeki K, Nakaya M, Takaesu G, Hori S, Yoshimura A, Kobayashi T
  • Journal Title: J Biol Chem. 283(25) Pages: 17003-17008
  • Peer Reviewed
• [Journal Article] STAT6 inhibits TGF-beta 1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. (2008)
  • Author(s): Takaki H, Ichiyama K, Koga K, Chinen T, Takaesu G, Sugiyama Y, Kato S, Yoshimura A, Kobayashi T
  • Journal Title: J Biol Chem. 283(22) Pages: 14955-14962
  • Peer Reviewed
• [Journal Article] Cutting edge : requirement for TRAF6 in the induction of T cell anergy. (2008)
  • Author(s): King CG, Buckler JL, Kobayashi T, Hannah JR, Bassett G, Kim T, Pearce EL, Kim GG, Turka LA, Choi Y
  • Journal Title: J Immunol. 180(1) Pages: 34-38
  • Peer Reviewed
• [Presentation] Loss of SOCS1 in B cells results in hyper IgE syndrome (HIES) and predisposes to allergy in mice. (2010)
  • Author(s): Takashi Kobayashi, Yuko Matsunaga, Miyuri Kawasumi, Satoru Fukuyama, Hiromasa Inoue, Akihiko Yoshimura
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-27
• [Presentation] Loss of SOCS1 in B cells results in hyper IgE syndrome (HIES) and predisposes to allergy in mice. (2010)
  • Author(s): Kobayashi T, et al.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe Portopia Hotel
• [Presentation] B細胞特異的SOCS1欠損マウスにみられる高IgE血症とアレルギー病態の解析 (2009)
  • Author(s): 小林隆志、松永悠子、川澄みゆり、福山聡、井上博雅、吉村昭彦
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2009-12-04
• [Presentation] B細胞特異的SOCS1欠損マウスにみられる高IgE血症とアレルギー病態の解析 (2009)
  • Author(s): 小林隆志, ほか
  • Organizer: 日本免疫学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-04
• [Presentation] RNAウイルス応答シグナルにおけるTRAF6および関連分子の役割 (2009)
  • Author(s): 小林隆志
  • Organizer: 第74回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-06-26
• [Presentation] TRAF6 Is Required for Generation of the B-1a B Cell Compartment as well as T Cell-Dependent and-Independent Humoral Immune Responses. (2009)
  • Author(s): Takashi Kobayashi, Anand Jacob, Tae Soo Kim, Miyuri Kawasumi, Akihiko Yoshimura, Masahiro Yamamoto, Tsuneyasu Kaisho, Shizuo Akira, Yongwon Choi
  • Organizer: The 1^<st> international Kishimoto foundation symposium, Immune Regulation : Present and Future
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2009-05-25
• [Presentation] TRAF6 Is Required for Generation of the B-1a B Cell Compartment as well as T Cell-Dependent and-Independent Humoral Immune Responses (2009)
  • Author(s): 小林隆志, et. al.
  • Organizer: The first International Kishimoto Foundation Symposium
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-05-25
• [Presentation] TRAF6 and MEKK1 Play Pivotal Roles in the RIG-like Helicase/IPS-1 Antiviral Pathway. (2008)
  • Author(s): Ryoko Yoshida, Akihiko Yoshimura, Takashi Kobayashi
  • Organizer: The 8^<th> Awaji International Forum on Infection and Immunity.
  • Place of Presentation: Awaji, Japan.
  • Year and Date: 2008-09-09
• [Book] 細胞工学(自己免疫疾患と炎症 29(8)) (2010)
  • Author(s): 永淵正法,塚本浩,新納宏昭,小林隆志
  • Publisher: 秀潤社
• [Book] アレルギー・免疫(感染症制御における制御性T細胞 vol.16(5)) (2009)
  • Author(s): 小林隆志、川澄みゆり、濱野真二郎
  • Publisher: 医薬ジャーナル社
• [Book] 臨床免疫・アレルギー科(TGF-β,IL-10を産生する抑制性ヘルパーT細胞の誘導とSTAT3/SOCS3による制御 vol.50(2)) (2008)
  • Author(s): 知念孝敏、金城市子、吉村昭彦、小林隆志
  • Publisher: 科学評論社
• [Book] 細胞工学(サイトカインによるTh17とiTregの分化制御 vol.27(2)) (2008)
  • Author(s): 吉村昭彦、知念孝敏、市山健司、小林隆志
  • Publisher: 秀潤社
• [Remarks] ホームページ等