生殖・神経環境におけるIgA/IgM抗体の機能

2007 Fiscal Year Annual Research Report

• Project/Area Number: 18060004
• Research Institution: University of Tsukuba
• Principal Investigator: 渋谷 彰 University of Tsukuba, 大学院・人間総合科学研究科, 教授 (80216027)
• Keywords: 液性免疫 / 免疫グロブリン受容体 / IgM / Fc受容体 / Fca / u受容体 / 補体

Research Abstract

抗原が生体内に侵入すると、免疫システムが作動し、B細胞が個々の抗原に特異的な抗体(免疫グロブリン)を分泌する。抗体は抗原と結合することによって修飾を受け免疫複合体を形成し、細胞性免疫を担うリンパ球、顆粒球、マクロファージなどの種々のエフェクター細胞とこれらの細胞に発現する免疫グロブリンFc受容体を介して結合することにより、これらの細胞の活性化を制御する。したがって抗体は抗原刺激に反応して分泌され、免疫グロブリン受容体を介して抗原情報をエフェクター細胞に伝えるシグナンレ伝達分子である。
申請者らは、IgMに対する受容体(Fcα/μ受容体)を世界に先駆けて同定した(Shibuya,et al.,Nature Immunology 2000、Shimizu,et al.,Immunogenetics 2001)。これは同時にIgAに対する受容体でもあった。申請者らは、Fcα/μ受容体が免疫組織の他に、中枢神経系、精巣に発現することを明らかにした(Sakamoto,et al.,Eur J Immunol 2001,Nakahera,et al,Neurosci Lett 2003)。したがって、これらの臓器、組織ではFcα/μ受容体がリガンドであるIgAあるいはIgMと結合して、高次生命統御機能を担っていることが考えられる。実際、Fcα/u受容体の遺伝子欠損マウスでは、完全な雄性不妊を示し、Fcα/μ受容体が精巣において重要な役割を担っていることを示している。
本年は、Fcα/μ受容体め遺伝子欠損マウスにおいてT非依存性抗原に対する液性免疫応答が亢進していることを明らかにした。これは補体依存性によるものであることも明らかにした。

Research Products

• [Journal Article] Caspase-independent cell death by CD300LF(MAIR-V),an inhibitory immunoglobulin-like receptor on myeloid cells (2008)
  • Author(s): Can, I, et. al.
  • Journal Title: Journal of Immunology 180:1 Pages: 207-13
  • Peer Reviewed
• [Journal Article] Unusal biochemical features and follicular dendritic cell expression of human Fcalpha/mu receptor. (2007)
  • Author(s): Kikuno, K, et. al.
  • Journal Title: Eur J Immunol 37 Pages: 3540-3550
  • Peer Reviewed
• [Journal Article] The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors (2007)
  • Author(s): Hara, H, et. al.
  • Journal Title: Nature Immunology 180:1 Pages: 207-13
  • Peer Reviewed
• [Journal Article] Activation of neutrophils by a novel triggering immunoglobulin-like receptor MAIR-IV. (2007)
  • Author(s): Nakano, T, et. al.
  • Journal Title: Molecular immunology 45(1) Pages: 289-94
  • Peer Reviewed
• [Journal Article] Dual assemblies of an activating immune receptor,MAIR-II,WITH itam-bearing adapters DAP12 and FcR chain on peritoneal macrophages. (2007)
  • Author(s): Nakahashi, C, et. al.
  • Journal Title: Journal of Immunology 15;178(2) Pages: 765-70
  • Peer Reviewed
• [Journal Article] A critical role of LFA-1 in the development of Th17 cells and induction of experimental autoimmune encephalomyelitis. (2007)
  • Author(s): Wang, Y, et. al.
  • Journal Title: Biochem Biophys Res Commun 23;355 Pages: 857-62
  • Peer Reviewed
• [Journal Article] Th1 and Type 1 Cytotoxic T Cells Dominate the Responses in Tbet Over expression Transgenic Mice that Develop Contact Dermatitis. (2007)
  • Author(s): Ishizaki, K, et. al.
  • Journal Title: Journal of Immunology 178(1) Pages: 605-12
  • Peer Reviewed
• [Journal Article] Expression of a Splicing Esoform of MAIR-V(CD300LF),an inhibitory immunoglobulin-like receptor on myeloid cells.
  • Author(s): Can, I, et. al.
  • Journal Title: Hybridoma In preess
  • Peer Reviewed
• [Presentation] Negative regulation of IgA production by the Fcα/μ recepto, an Fc receptor for IgA and IgM. (2008)
  • Author(s): KURITA, Naoki・HONDA, Shin-ichiro・CHO, Yukiko・USUI, Kenta・TAKESHITA Kie・TAHARA-HANAOKA, Satoko・SHIBUYA, Kazuko・SHIBUYA, Akira
  • Organizer: 第3回JSI-RCAI免疫ワークショップ
  • Place of Presentation: 理化学研究所・横浜研究所
  • Year and Date: 2008-03-14
• [Presentation] Activation of neutrophils by a novel triggering immunoglobulin-like receptor MAIR-IV (2008)
  • Author(s): Takako, Nakano・Satoko, Tahara-Hanaoka・Chigusa, Nakahashi-Oda・Ismail, Can・Naoya, Totsuka・Kaori, Hitomi・Satoru, Someya・Shin-ichiro, Honda・Kazuko, Shibuya・Akira, Shibuya
  • Organizer: Keystone Symposia.
  • Place of Presentation: Keystone USA
  • Year and Date: 2008-02-25
• [Presentation] IgM suppresses humoral immune responses against T-independen antigens via the Fcα/μR (2007)
  • Author(s): HONDA, Shin-ichiro・CHO Yukiko・USUI Kenta・KURITA, Naoki・TAKESHITA, Kie1・TAKAHASHI Satoru・KINOSHITA Taroh・FUJITA, Teizo・TAHARA-HANAOKA, Satoko・SHIBUYA, Kazuko・SHIBUYA, Akira
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] Caspase-independent cell death by MAIR-V(CD300LF), immunoglobulin-like receptor onmyeloid cells (2007)
  • Author(s): Ismail, Can・Satoko, Tabara-Hanaoka・Shin-ichiro, Honda・Kazuko, Shibuya・Akira, Shibuya.
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] A critical role of DNAM-1 in tumor immunosurveillance (2007)
  • Author(s): Iguchi, Akiko・SHIBUYA Kazuko・KAI Hirayasu・TAHARA-HANAOKA Satoko・HONDA, Shinichiro・SHIBUYA, Akira.
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] analysis for the variants of Fcα/μR, a novel Fc receptor for IgA and IgM, expressed in the kidney and testis. (2007)
  • Author(s): USUI, Kenta・HONDA, Shin-ichiro・KURITA, Naoki・MIYAMOTO, Akitomo・CHO, Yukiko・TAHARA-HANAOKA, Satoko・SHIBUYA, Kazuko・SHIBUYA, Akira
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] Negative regulation of IgA production by the Fcα/μ recepto, an Fc receptor for IgA and IgM. (2007)
  • Author(s): KURITA, Naoki・HONDA, Shin-ichiro・CHO, Yukiko・USUI, Kenta・TAKESHITA Kie・TAHARA-HANAOKA, Satoko・SHIBUYA, Kazuko・SHIBUYA, Akira
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] A critical role of LFA-1 in the development of Th17 cells and induction of experimental autoimmune encep halomyelitis. (2007)
  • Author(s): SHIBATA, Kai1・WANG, Yinan1・KAI, Hirayasu1・TAHARA-HANAOKA, Satoko1・HONDA, Shin-ichiro1・SHIBUYA, Kazuko.
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] Critical role of DNAM-1(CD226) in the development of Th1 cells. (2007)
  • Author(s): KAI, Hirayasy・IGUCHI, Akiko・WANG, Yinan・YAMASHITA, Yumi・YASUI, Teruhito・KIKUTANI, Hitoshi・THARA-HANAOKA, Satoko・HONDA, sHIN-ichiro・SHIBUYA, Akira・SHIBUYA, Kazuko
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] A novel triggering neutrophil receptor, MAIR-IV, transduces activating signal via FcRγ-independent as well as dependent pathways. (2007)
  • Author(s): Takako, Nakano・Satoko, Tahara-Hanaoka・Chigusa, Nakahashi-Oda・Ismail, Can・Naoya, Totsuka・Kaori, Hitomi・Satoru, Someya・Shin-ichiro, Honda・Kazuko, Shibuya・Akira, Shibuya
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] ITIM-bearing Immunoglobulin-like receptor, MAIR-I(CD300a)modulates the inflammatory responses in murine sepsis. (2007)
  • Author(s): Chigusa, Nakahashi-Oda・Satoko, Tahara-Hanaoka・Kaori, Hitomi・Takako, Nakano・Can Ismail・Naoya, Totsuka・Teruhito, Yasui・Hitoshi, Kikutani・Shin-ichiro, Hond・Kazuko, Shibuya・Akira, Shibuya
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] Molecular characterization of Fcα/μR, a movel Fc receptor for IgA and IgM. (2007)
  • Author(s): CHO, Yukiko・HONDA, Shin-ichiro・USUI, Kenta・KURITA, Naoki・TAKESHITA, Kie・TAHARA-HANAOKA, Satoko・SHIBUYA, Kazuko・SHIBUYA, Akira.
  • Organizer: 第37回 日本免疫学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20071120-22
• [Presentation] 精子細胞分化におけるFcα/μRの役割 (2007)
  • Author(s): 臼井健太・本多伸一郎・渋谷彰
  • Organizer: 特定領域研究「生殖細胞の発生プロセス・再プログラム化とエピジェネティクス」公開シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-11-02
• [Presentation] ITIMを持つ免疫受容体MAIR-Vの機能解析 (2007)
  • Author(s): Ismail, Can・Satoko, Tabara-Hanaoka・Shin-ichiro, Honda・Kazuko, Shibuya・Akira, Shibuya.
  • Organizer: 第69回 日本地液学会
  • Place of Presentation: 神奈川
  • Year and Date: 2007-10-12
• [Presentation] 好中球の活性化を制御する新規ペア型受容体MAIR-IV (2007)
  • Author(s): 中埜貴子・田原聡子・中橋ちぐさ・Ismail, Can・戸塚直也・本多伸一郎・渋谷和子・渋谷彰
  • Organizer: 第69回 日本地液学会
  • Place of Presentation: 神奈川
  • Year and Date: 2007-10-12
• [Presentation] Control of Germinal Center Reaction against TIndependent Antigens by the Fc(alpha)/(mu) receptor. (2007)
  • Author(s): Akira Shibuya.
  • Organizer: 13th International Congress of Immunology
  • Place of Presentation: Rio de Janeiro-Brazil
  • Year and Date: 2007-08-21
• [Presentation] ヘルパーT細胞免疫応答におけるDNAM-1の役割 (2007)
  • Author(s): 甲斐平康・渋谷和子・井口研子・田原聡子・本多伸一郎・渋谷彰
  • Organizer: KTCC
  • Place of Presentation: 京都
  • Year and Date: 2007-06-16
• [Presentation] Control of Germinal Center Reaction against TIndependent Antigens by the Fc(alpha)/(mu)Receptor. (2007)
  • Author(s): Akira, Shibuya・Ukiko, Cho・Satoko, Tahara-Hanaoka・kazuko, Shibuiya・Shin-ichiro Honda
  • Organizer: 94th Annual Meeting The American Association of Immunologists
  • Place of Presentation: USA
  • Year and Date: 2007-05-21
• [Presentation] Physical and functional association of MAIR-II with ITAM containing a dapters FcRγ chain as well as DAP12 in activated macrophages. (2007)
  • Author(s): A, Shibuya・C, Nakahashi・N, Totsuka・S, Tahara-Hanaoka
  • Organizer: Keystone Symposia
  • Place of Presentation: Colorado, USA
  • Year and Date: 2007-04-12