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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アレルギー / B細胞 / シグナル伝達 / IgE / 可視化 / 制御性T細胞

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] Dengue transmission model by means of viremic adult immuno-competent mouse (2014)
  • Author(s): Lucky Ronald Runtuwene, Eiji Konishi, Atsushi Yamanaka, Yoshihiro Makino, Yutaka Suzuki, Tomohiko Takasaki, Ichiro Kurane, Takashi Kobayashi and Yuki Eshita
  • Journal Title: Parasites & Vectors Volume: 7 Issue: 1 Pages: 143-143
  • DOI: 10.1186/1756-3305-7-143
  • Peer Reviewed / Open Access
• [Journal Article] Vector competence of Aedes aegypti to dengue virus. (2014)
  • Author(s): Lucky Ronald Runtuwene, Kaori Noguchi, Akinori Tokunaga, Takashi Kobayashi, Kenta Nakai and Yuki Eshita
  • Journal Title: Urban Pest Management Volume: 4 (1)
  • NAID: 110009818404
  • Peer Reviewed
• [Journal Article] DEAE－デキストラン－MMA グラフト共重合体をホストとして用い、ゲストのパクリタキセルと成る、超分子複合体－その人工酵素、抗癌メカニズム (2014)
  • Author(s): 大西 靖彦・江下 優樹・紀 瑞成・小林隆志・大西 政康・水野 正明・吉田 純・久保田 直治
  • Journal Title: 大分大学工学部研究報告 Volume: -
  • NAID: 120005539559
  • Peer Reviewed
• [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)
  • 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] 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) Issue: 1 Pages: 19-25
  • DOI: 10.1016/j.gene.2013.08.015
  • Peer Reviewed
• [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) Issue: 9 Pages: e74639-e74639
  • DOI: 10.1371/journal.pone.0074639
  • Peer Reviewed
• [Journal Article] Multiple infections with helminthes -whipworm, hookworm, and roundworm (2013)
  • Author(s): Kunimitsu Inoue, Sotaro Ozaka, Kazuhisa Okamoto, Ryu Ogawa, Kazuhiro Mizukami, Tadayoshi Okimoto, Masaaki Kodama, Takashi Kobayashi, Yuki Eshita, Hideo Hasegawa, Kazunari Murakami
  • Journal Title: Endoscopy Volume: 46 Issue: S 01 Pages: 117-118
  • DOI: 10.1055/s-0034-1364887
  • Peer Reviewed / Open Access
• [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): Yuki Eshita, Rui-Cheng Ji, Masayasu Onishi, Lucky Ronald Runtuwene, Kaori Noguchi, Takashi Kobayashi, Masaaki Mizuno, Jun Yoshida, Naoji Kubota and Yasuhiko Onishi
  • Journal Title: J. Nanomed. Biotherapeut. Discov. Volume: 2 Issue: 05 Pages: 109-109
  • 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
  • NAID: 10031166054
  • 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
• [Journal Article] Aberrant IL-4 production by SOCS3-overexpressing T cells during infection with Leishmania major exacerbates disease manifestations (2011)
  • Author(s): Nakaya, M., Hamano, S., Yoshida, H., Yoshimura, A., Kobayashi, T.
  • Journal Title: Int.Immunol. Volume: 23 Issue: 3 Pages: 195-202
  • DOI: 10.1093/intimm/dxq472
  • 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 Issue: 12 Pages: 10641-10648
  • DOI: 10.1074/jbc.m110.216390
  • Peer Reviewed
• [Journal Article] Osteoclasts are dispensable for haematopoietic stem cell maintenance and mobilization (2011)
  • Author(s): Miyamoto K, et al
  • Journal Title: J Exp Med Volume: 208 Issue: 11 Pages: 2175-2181
  • DOI: 10.1084/jem.20101890
  • Peer Reviewed
• [Journal Article] IL-1β and TNFα-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis (2011)
  • Author(s): Mori T, et al
  • Journal Title: Int Immunol Volume: 23 Issue: 11 Pages: 701-712
  • DOI: 10.1093/intimm/dxr077
  • Peer Reviewed
• [Journal Article] TGF-beta-Activated Kinase 1 (TAK1)-Bmding Proteins (TAB) 2 and 3 Negatively Regulate Autophagy (2011)
  • Author(s): Takaesu G, Kobayashi T, Yoshimura A
  • Journal Title: J Biochem. Volume: 151 Issue: 2 Pages: 157-166
  • DOI: 10.1093/jb/mvr123
  • Peer Reviewed
• [Journal Article] 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
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56 Pages: 151-158
• [Presentation] 本邦産Aedes (Stegomyia) scutellarisグループ蚊2種のチクングニアウイルス感受性(2) (2014)
  • Author(s): 江下優樹, 福田昌子, Lucky Runtuwene, 大塚 靖, 野口香緒里, 川上絵理, 德永暁憲, 小林隆志, 服部正策, Raweewan Srisawat, Narumon Komalamisra, 牛島廣治, 倉根一郎, 高崎智彦
  • Organizer: 第66回日本衛生動物学会大会
  • Place of Presentation: 岐阜大学地域科学部、岐阜県岐阜市
• [Presentation] Utilization of CCL-125 for analyzing innate immunity in Aedes aegypti (2014)
  • Author(s): Lucky R. Runtuwene, Shuichi Kawashima, Kaori Noguchi, Eri Kawakami, Akinori Tokunaga, Yutaka Suzuki , Sumio Sugano, Kenta Nakai, Ryuichiro Maeda, Chihiro Sugimoto, Tomohiko Takasaki, Ichiro Kurane, Takashi Kobayashi and Yuki Eshita
  • Organizer: 第66回日本衛生動物学会大会
  • Place of Presentation: 岐阜大学地域科学部、岐阜県岐阜市
• [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
• [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
• [Presentation] 節足動物媒介性ウイルスの迅速検出へのRT-LAMP法の改良 (2013)
  • Author(s): 江下優樹,松原祥恵,Lucky R.Runtuwene,野口香緒里,川上絵理,大塚 靖,福田昌子,小林隆志,高崎智彦,Raweewan Srisawat,Narumon Komalamisra,Bouasy Hongvanthong,成田弘成,牛島廣治,Arthur E. Mongan,今田美穂子,前田龍一郎,森田公一,杉本千尋,倉根一郎
  • Organizer: 日本家屋害虫学会
  • Place of Presentation: 日本大学生物資源科学部、神奈川県藤沢市
• [Presentation] INOVATIVE TECHNOLOGY FOR USE IN VECTOR CONTROL (2013)
  • Author(s): Yuki Eshita, Lucky R. Runtuwene, Masako Fukuda, Yasushi Otsuka, Akinori Tokunaga, Takashi Kobayashi, Raweewan Srisawat, Bouasy Hongvanthong, Arthur E. Mongan, Josef Tuda, Mihoko Imada, Tomohiko Takasaki, Ichiro Kurane, et al.
  • Organizer: The 1st conference on asian pediatric infectious diseases
  • Place of Presentation: 東京大学医学部3号館N101室、東京都文京区
• [Presentation] Comprehensive Gene Expression Analysis of Dengue-Infected Mosquitoes (2013)
  • Author(s): Lucky Runtuwene, Shuichi Kawashima, Kaori Noguchi, Eri Kawakami, Akinori Tokunaga, Yutaka Suzuki, Takashi Kobayashi, Yuki Eshita
  • Organizer: The 1st conference on asian pediatric infectious diseases
  • Place of Presentation: 東京大学医学部3号館N101室、東京都文京区
• [Presentation] Comprehensive gene expression analysis of dengue-infected Aedes aegypti and novel anti-viral proteins in Aedes aegypti (2013)
  • Author(s): Lucky Runtuwene, Shuichi Kawashima, Kaori Noguchi, Eri Kawakami, Akinori Tokunaga, Junya Yamagishi, Mihoko Imada, Ryuichiro Maeda, Yutaka Suzuki, Takashi Kobayashi, Yuki Eshita
  • Organizer: インドネシア国寄生虫会議セミナー
  • Place of Presentation: インドネシア国マナド市サムラトランギ大学
• [Presentation] 本邦産Aedes (Stegomyia) scutellarisグループ蚊2種のチクングニアウイルス感受性 (2013)
  • Author(s): 江下優樹、福田昌子、Lucky Runtuwene、大塚 靖、野口香緒里、川上絵理、德永暁憲、小林隆志、服部正策、Raweewan Srisawat、Narumon Komalamisra、牛島廣治、倉根一郎、高崎智彦
  • Organizer: 第66回日本寄生虫学会南日本支部大会・第63回日本衛生動物学会南日本支部大会 合同大会
  • Place of Presentation: 大分県由布市、大分大学医学部臨床講義棟1F 臨床中講義室
• [Presentation] Potential novel anti-viral proteins in Aedes aegypti (2013)
  • Author(s): Lucky Runtuwene, Shuichi Kawashima, Kaori Noguchi, Eri Kawakami, Akinori Tokunaga, Yutaka Suzuki, Takashi Kobayashi, Yuki Eshita
  • Organizer: 第66回日本寄生虫学会南日本支部大会・第63回日本衛生動物学会南日本支部大会 合同大会
  • Place of Presentation: 大分県由布市、大分大学医学部臨床講義棟1F 臨床中講義室
• [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回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ、千葉県千葉市
• [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
• [Presentation] Analysis of molecular mechanisms underlying hyper production of IgE in B cell-specific SOCS1 deficient mice. (2011)
  • Author(s): Shinya Hidano, Akihiko Yoshimura, and Takashi Kobayashi
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Regulatory T cells specific TRAF6 deletion resulted in Th2 type inflammation. (2011)
  • Author(s): Go Muto, Takashi Kobayashi, Akihiko Yoshimura.
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [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.
  • 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
  • Place of Presentation: 福岡市
• [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.
  • 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
  • Place of Presentation: 福岡市
• [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
• [Remarks]
  • URL: http://www.med.oita-u.ac.jp/idc/
• [Remarks] 大分大学医学部感染予防医学講座のホームページ
  • URL: http://www.med.oita-u.ac.jp/idc/index.html