精子細胞分化におけるFcα/μRの役割

• Project/Area Number: 18051002
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• 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)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥7,200,000 (Direct Cost: ¥7,200,000); Fiscal Year 2007: ¥3,600,000 (Direct Cost: ¥3,600,000); Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
• Keywords: Fcα / μR / IgA / IgM / 精巣 / 不妊

Research Abstract

我々は最近、IgMに対する受容体(Fcα/μR)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。Fcα/μRのmRNAは免疫組織の他に、神経系、精巣に発現を認めた(Sakamoto, et al., Eur J Immunol,2001)。申請者らはFcα/μRの生体内機能を明らかにする目的で、Fcα/μRの遺伝子欠損マウスを作製した。ホモ遺伝子欠損マウス(Fcα/μR-/-)はメンデルの法則に従って産まれてきたが、全く予期せぬことに、オスFcα/μR-/-は完全な不妊を呈した。しかしメスFcα/μR-/-の生殖能に異常はなかった。そこで、不妊の原因を明らかにするために、Fcα/μR-/-の精巣の組織学的解析をしたところ、精子の各分化ステージで野生型にはみられない伸長精子細胞の頭部の形態異常がみられ、正常な頭部を有した精子が観察されず、精巣上体頭部から尾部にかけての精子の貯留もみられなかった。以上の結果からFcα/μRr-/-マウスでは精子細胞の分化異常により不妊を呈するものと考えられた。
本研究では、Fcα/μRのmRNAの発現をPCRで解析するとともに、Fcα/μRの蛋白レベルでの発現を抗Fcα/μRモノクローナル抗体(TX57)を用いて解析した。その結果、Fcα/μRは未熟な精子細胞に発現することを明らかにした。

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] Unusual 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;353 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] 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: Jornal of Immunology 15;178(2) Pages: 765-770
• [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;353(4) Pages: 857-862
• [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: Jornal of Immunology 15;178(2) Pages: 765-770
• [Journal Article] Molecular and functional characteristics of the Fcα/μR, a novel Fc receptor for IgM and IgA. (2006)
  • Author(s): Shibuya A et al.
  • Journal Title: Seminar in Immunohistopathol 28 Pages: 377-382
• [Journal Article] Molecular characteristics of IgA and IgM Fc binding to the Fcalpha/muR. (2006)
  • Author(s): Cho Y et al.
  • Journal Title: Biochem Biophys Res Commun. Jun 23;345(1) Pages: 474-478
• [Journal Article] A carbohydrate binding protein Galectin-1, promotes proliferation of adult neural stem cells. (2006)
  • Author(s): Sakaguchi M et al.
  • Journal Title: Proc Natl Acad Sci USA May 2;103(18) Pages: 7112-7117
• [Journal Article] LFA-1-dependent lipid rafts recruitment of DNAM-1 (CD226) in CD4+ T cell. (2006)
  • Author(s): Shirakawa J et al.
  • Journal Title: Int Immunol 18(6) Pages: 951-957
• [Journal Article] Critical role of M. tuberculosis for dendritic cell maturation to induce collagen-induced arthritis in H-2b background of C57BL/6 mice. (2006)
  • Author(s): Kai H et al.
  • Journal Title: Immunology 118 Pages: 233-239
• [Journal Article] A specific CpG demethylation in the human IL-2 gene promoter as an epigenetic memory. (2006)
  • Author(s): Murayama A et al.
  • Journal Title: EMBO J 25 Pages: 1081-1092
• [Journal Article] Comment on"CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions" (2006)
  • Author(s): Shibuya K et al.
  • Journal Title: Jornal of Immunology 176 Pages: 3855-3855
• [Journal Article] Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor (2006)
  • Author(s): Tahara-Hanaoka S et al.
  • Journal Title: Blood 107 Pages: 1491-1796
• [Presentation] IgM suppresses humoral immune responses against T-independent 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
• [Presentation] Analysis for the variants of Fcα/μR,a novel Fcreceptor 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
• [Presentation] Negative regulation of IgA production by the Fcα/μrecepto,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
• [Presentation] A critical role of LFA-1 in the development of Th17cells and induction of experimental autoimmune encephalomyelitis. (2007)
  • Author(s): SHIBATA, Kai1・WANG, Yinan1・KAI, Hirayasu1・TAHARA-HANAOKA, Satoko1・HONDA, Shim-ichiro1・SHIBUYA, Akira1・SHIBUYA, Kazuko.
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Critical role of DNAM-1(CD226) in the development of Th1 cells. (2007)
  • Author(s): KAI, Hirayasy・ICUCHI, 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
• [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, Nakabashi-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
• [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, Tostuka・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
• [Presentation] Molecular characterization of Fcα/μR,a novel Fc receptor for IgA and IgM. (2007)
  • Author(s): CHO, Yukiko・HONDA, Shin-ichiro・USUI, Kenta・KURITA, Naok・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