Molecular and cellular mechanism controlling IgE-producing B cells that contributes to the pathogenesis of allergic diseases.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Oita University (2012-2013); Keio University (2011)
• Principal Investigator: KOBAYASHI Takashi 大分大学, 医学部, 教授 (30380520)
• Project Period (FY): 2011 – 2013
• Keywords: アレルギー / B細胞 / シグナル伝達 / IgE

Research Abstract

B cell-specific disruption of SOCS1 which is a suppressor of cytokine signaling in mice results in the elevation of serum IgE levels. Homozygous deletion of SOCS1 gene in B cells enhanced the susceptibility to development of allergen-induced airway inflammation, allergic rhinitis and otitis media, but not the development of germinal center B cells or memory B cells. On the other hand, Treg-specific TRAF6 deficient mice dramatically increased Th2 cytokine production leading to the hyper IgE syndrome, and developed allergic skin diseases, arthritis, lymphadenopathy. These results suggest that both SOCS1 and TRAF6 may contribute to the pathogenesis of allergic diseases.

Research Products

• [Journal Article] TRAF6 Is Essential for Maintenance of Regulatory T Cells That Suppress Th2 Type Autoimmunity (2013)
  • Author(s): Muto G, Kotani H, Kondo T, Morita R, Tsuruta S, Kobayashi T, Luche H, Fehling HJ, Walsh M, Choi Y, Yoshimura A
  • Journal Title: PLoS One Volume: 8(9) Pages: e74639
  • Peer Reviewed
• [Journal Article] Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b (2013)
  • Author(s): Matsuo T, Noguchi Y, Shindo M, Morita Y, Oda Y, Yoshida E, Hamada H, Harada M, Shiokawa Y, Nishida T, Tominaga R, Kikushige Y, Akashi K, Kudoh J, Shimizu N, Tanaka Y, Umemura T, Taniguchi T, Yoshimura A, Kobayashi T, Mitsuyama M, Kurisaki H, Katsuta H, Nagafuchi S
  • Journal Title: Gene Volume: 530(1) Pages: 19-25
  • Peer Reviewed
• [Journal Article] Supramolecular Targeting of B16F10 Melanoma Cells With Nanoparticles Consisting of a DEAE-Dextran-MMA Copolymer-Paclitaxel Complex In vivo and In vitro (2012)
  • Author(s): Eshita Y, Ji RC, Onishi M, Runtuwene LR, Noguchi K, Kobayashi T, Mizuno M, Yoshida J, Kubota N, Onishi Y
  • Journal Title: J Nanomed Biotherapeut Discov Volume: 2 Pages: 109
  • DOI: 10.4172/2155-983X.1000109
  • Peer Reviewed
• [Journal Article] Positive regulation of osteoclastic differentiation by growth differentiation factor-15 up-regulated in osteocytic cells under hypoxia (2012)
  • Author(s): Hinoi E, Ochi H, Takarada T, Nakatani E, Iezaki T, Nakajima H, Fujita H, Takahata Y, Hidano S, Kobayashi T, Takeda S, Yoneda Y
  • Journal Title: J Bone Miner Res Volume: 27(4) Pages: 938-949
  • Peer Reviewed
• [Journal Article] TGFβ-Activated Kinase 1 (TAK1)-Binding Proteins (TAB) 2 and 3 Negatively Regulate Autophagy (2011)
  • Author(s): Takaesu G, Kobayashi T, Yoshimura A
  • Journal Title: J Biochem Volume: 151(2) Pages: 157-166
  • Peer Reviewed
• [Journal Article] IL-1beta and TNFalpha-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis (2011)
  • Author(s): Mori T, Miyamoto T, Yoshida H, Asakawa M, Kawasumi M, Kobayashi T, Morioka H, Chiba K, Toyama Y, Yoshimura A
  • Journal Title: Int Immunol Volume: 23(11) Pages: 701-712
  • Peer Reviewed
• [Journal Article] Osteoclasts are dispensable for haematopoietic stem cell maintenance and mobilization (2011)
  • Author(s): Miyamoto K, Yoshida S, Kawasumi M, Hashimoto K, Kimura T, Sato Y, Kobayashi T, Miyauchi Y, Hoshi H, Iwasaki R, Miyamoto H, Hao W, Morioka H, Chiba K, Kobayashi T, Yasuda H, Penninger JM, Toyama Y, Suda T and Miyamoto T
  • Journal Title: J Exp Med Volume: 208(11) Pages: 2175-2181
  • Peer Reviewed
• [Journal Article] A germ cell specific gene, Prmt5 works as somatic cell reprogramming (2011)
  • Author(s): Nagamatsu G, Kosaka T, Kawasumi M, Kinoshita T, Takubo K, Akiyama H, Sudo T, Kobayashi T, Oya M, and Suda T
  • Journal Title: J Biol Chem Volume: 286(12) Pages: 10641-10648
  • 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, Hamano S, Kawasumi M, Yoshida H, Yoshimura A, Kobayashi T
  • Journal Title: Int Immunol Volume: 23 Pages: 195-202
  • Peer Reviewed
• [Presentation] The effects of allergic rhinitis on mucosal immunity of the middle ear in B cell-specific SOCS1 deficient mice (2013)
  • Author(s): Kaori Noguchi, Toshiaki Kawano, Takashi Hirano, Yoshinori Kadowaki, Masashi Suzuki, Takashi Kobayashi
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 20131200
• [Presentation] Analysis of the mucosal immune system of middle ear and nose in Suppressor of cytokine signaling (SOCS)-1 knockout mouse model with allergic rhinitis (2013)
  • Author(s): Toshiaki Kawano, Takashi Hirano, Yoshinori Kadowaki, Munehito Moriyama, Tarou Iwasaki, Kaori Noguchi, Takashi Kobayashi, Masashi Suzuki
  • Organizer: The 7th Extraordinary International symposium on recent advances in otitis media
  • Place of Presentation: Stockholm, Sweden
  • Year and Date: 20130612-16
• [Presentation] 新規蛍光・化学発光プローブSuperSTAR遺伝子を用いた組織特的レポーターマウスの開発 (2012)
  • Author(s): 小林隆志,原央子,飛彈野真也,野口香緒里,中野雅裕,永井健治,岡野ジェイムス洋尚,岡野栄之
  • Organizer: 第35回日本分子生物学会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] IL-10受容体に結合する候補分子Zimp7の細胞内局在と機能の解析 (2012)
  • Author(s): 野口香緒里,佐藤翔太,石川天洋,徳永暁憲,小林隆志
  • Organizer: 第35回日本分子生物学会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] Regulatory T cells specific TRAF6 deletion resulted in Th2 type inflammation (2011)
  • Author(s): Go Muto, Takashi Kobayashi, Akihiko Yoshimura
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉幕張メッセ(千葉)
  • Year and Date: 2011-11-29
• [Presentation] Analysis of molecular mechanisms underlying hyper production of IgE in B cell-specific SOCS1 deficient mice (2011)
  • Author(s): Shinya Hidano, Akihiko Yoshimura, Takashi Kobayashi
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉幕張メッセ(千葉)
  • Year and Date: 2011-11-29
• [Book] 臨床免疫・アレルギー科vol.56 (2), サイトカインシグナル抑制因子SOCSによるIgE産生の制御 (2011)
  • Author(s): 小林隆志、飛彈野真也
  • Total Pages: 151-158
• [Remarks]
  • URL: http://www.med.oita-u.ac.jp/idc/