2000 年度実績報告書

微生物の感染が誘導するヒト樹状細胞遺伝子群の網羅的解析

研究課題

研究課題/領域番号	12206087
研究機関	大阪府立成人病センター研究所
研究代表者	瀬谷司大阪府立成人病センター研究所, 第6部・免疫, 部長 (10301805)
研究分担者	松本美佐子大阪府立成人病センター研究所, 第6部・免疫, 主任研究員 (30332456)
キーワード	Toll-like receptor / 樹状細胞 / innate immunity / subtraction screening / differential display / 抗原提示
研究概要	Genome projectが進行するにつれ、微生物由来の遺伝子断片がヒト・マウスにも多数存在し、機能するもの、可動性のものも含めて500以上見い出されることが判明した。これらはミトコンドリア(かつて独立のprokaryoteであった)などの由来に限定しない。進化は感染と宿主防衛の抗争史であった。感染に対抗する宿主側の要因として,既成の「免疫系」よりprimitiveな生体防御系・innate immunityがハエからヒトにまで普遍的な系として最近見出された。この系はToll-like receptor(TLR)familyからなる。TLRとは宿主細胞に存在して微生物に特有な成分を見分けるレセプター(パターン認識レセプター)で、直接の細胞応答で侵入微生物を排除する。ヒトの抗原提示細胞は、微生物成分/TLRによって成熟化し、リンパ球を活性化する。既成の免疫系とはこのinnate immunityの先行的活性化の産物と言える。パターン認識レセプターについてはgenome projectの情報のみが先行している状況である。その機能、活性化の分子機構,リガンド同定は今後の問題である。微生物成分の多様性に対応して認識レセプターがgenome levelで保持されているとの予測があるが,実証的な解析がなされたものは極めて限られる。ヒトではさらに不明の事項が多い。ヒト樹状細胞のTLR刺激前後の抗原提示細胞から遺伝情報を槐集し差をとれば、微生物への生体防御に関与する遺伝子の基礎資料を体系化できるはずである。申請者はTLRを活性化するBCG成分をTLR ligandとしてこの1年で生体防御に関与する遺伝子群約120をリストした。このほかに未報告のヒト遺伝子約30を得ており、機能解析中である。

研究成果
(16件)

すべてその他

すべて文献書誌 (16件)

[文献書誌] Begum,N.A. et al: "A BCG-CWS-regulated gene in human monocytes by differential display : Identification of a human homologue of chicken MD-1."Biochem.Biophys.Res.Commun.. 256. 325-329 (1999)
[文献書誌] Seya,T. et al: "Innate immune therapy for cancer : seeking for effective molecules for activation of the innate immune system (review)."Adv.Exp.Med.Biol.. 465:. 229-237 (1999)
[文献書誌] Tsuji,S. et al: "Maturation of human human dendritic cells by cell-wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin : involvement of Tolllike receptors"Infect.Immun.. 68. 6883-6890. (2000)
[文献書誌] Nomura,M et al: "Mechanism of gene regulation of membrane cofactor protein (CD46) in mice : Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene."Biochem.J.. 351:. 353-365 (2000)
[文献書誌] Inoue,N. et al: "A novel chicken membrane-associated complement-regulatory protein : Molecular cloning and functional characterization of a chicken membrane SCR protein."J.Immunol.. 166. 424-431 (2001)
[文献書誌] Nishiguchi,M., et al: "Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2 : Role of N-terminal hydrophobic portion in its multiple functions."J.Immunol. 166. 2610-2616 (2001)
[文献書誌] Nomura,M et al: "Gnomic analysis of ideopathic infertile patients with sperm-specific depletion of CD46."Exp.Clin.Immunogen. 18. 42-50 (2001)
[文献書誌] Matsumoto,M et al: "IFNg-producing ability in blood of patients with lung cancer : production of IL-12 p40 and IL-18 in response to BCG-CWS"Immunopharmacology. (in press).. (2001)
[文献書誌] Seya T. (one of the 96 authors): "Functional annotation of a full-length mouse cDNA collection. The RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium.Functional annotation meeting."Nature. 409. 685-690 (2001)
[文献書誌] Shida,K et al: "An alternative form of human IL-18 in human blood plasma : complex formation with IgM defined by monoclonal antibodies."J.Immunol. (in press).. (2001)
[文献書誌] Kikkawa,S et al: "Human macrophages produce dimeric forms of IL-18 which can be detected with monoclonal antibodies specific for inactive IL-18."Biochem.Biophys.Res.Commun.. 281. 461-467 (2001)
[文献書誌] Moriwaki,Y et al: "Identification and characterization of a novel BCG-inducible lysosomal membrane protein which finds the missing link between LITAF (PIG7) and EET-1."J.Biol.Chem.. (in press). (2001)
[文献書誌] Seya,T et al: "Two receptor theory in innate immune activation : studies on the receptors for bacillus Culmet Guillen-cell wall skeleton (BCG-CWS) (review)."Arch.Immunol.Ther.Exp.. (in press). (2001)
[文献書誌] Seya,T et al: "CD46 : membrane cofactor protein of complement and a measles virus receptor (review)."Encyclopedia of Molecular Medicine Ed.by T.E.Creighton.John Wiley & Sons, Inc.New York, NY pp. (in press).. (2001)
[文献書誌] Begum,N.A et al: "Molecular mechanisms of activation of the human innate immune system (review)."Cur.Trends Immunol.. (in press).. (2001)
[文献書誌] Azuma,I.and T.Seya.: "Cell wall skeleton of BCG : application to adjuvant immunotherapy for cancer (review)."Immunopharmacology. (in press).. (2001)

2000 年度 実績報告書

微生物の感染が誘導するヒト樹状細胞遺伝子群の網羅的解析

研究代表者

瀬谷 司 大阪府立成人病センター研究所, 第6部・免疫, 部長 (10301805)

研究成果

[文献書誌] Begum,N.A. et al: "A BCG-CWS-regulated gene in human monocytes by differential display : Identification of a human homologue of chicken MD-1."Biochem.Biophys.Res.Commun.. 256. 325-329 (1999)

[文献書誌] Seya,T. et al: "Innate immune therapy for cancer : seeking for effective molecules for activation of the innate immune system (review)."Adv.Exp.Med.Biol.. 465:. 229-237 (1999)

[文献書誌] Tsuji,S. et al: "Maturation of human human dendritic cells by cell-wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin : involvement of Tolllike receptors"Infect.Immun.. 68. 6883-6890. (2000)

[文献書誌] Nomura,M et al: "Mechanism of gene regulation of membrane cofactor protein (CD46) in mice : Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene."Biochem.J.. 351:. 353-365 (2000)

[文献書誌] Inoue,N. et al: "A novel chicken membrane-associated complement-regulatory protein : Molecular cloning and functional characterization of a chicken membrane SCR protein."J.Immunol.. 166. 424-431 (2001)

[文献書誌] Nishiguchi,M., et al: "Mycoplasma fermentans lipoprotein M161Ag-induced cell activation is mediated by Toll-like receptor 2 : Role of N-terminal hydrophobic portion in its multiple functions."J.Immunol. 166. 2610-2616 (2001)

[文献書誌] Nomura,M et al: "Gnomic analysis of ideopathic infertile patients with sperm-specific depletion of CD46."Exp.Clin.Immunogen. 18. 42-50 (2001)

[文献書誌] Matsumoto,M et al: "IFNg-producing ability in blood of patients with lung cancer : production of IL-12 p40 and IL-18 in response to BCG-CWS"Immunopharmacology. (in press).. (2001)

[文献書誌] Seya T. (one of the 96 authors): "Functional annotation of a full-length mouse cDNA collection. The RIKEN Genome Exploration Research Group Phase II Team and the FANTOM Consortium.Functional annotation meeting."Nature. 409. 685-690 (2001)

[文献書誌] Shida,K et al: "An alternative form of human IL-18 in human blood plasma : complex formation with IgM defined by monoclonal antibodies."J.Immunol. (in press).. (2001)

[文献書誌] Kikkawa,S et al: "Human macrophages produce dimeric forms of IL-18 which can be detected with monoclonal antibodies specific for inactive IL-18."Biochem.Biophys.Res.Commun.. 281. 461-467 (2001)

[文献書誌] Moriwaki,Y et al: "Identification and characterization of a novel BCG-inducible lysosomal membrane protein which finds the missing link between LITAF (PIG7) and EET-1."J.Biol.Chem.. (in press). (2001)

[文献書誌] Seya,T et al: "Two receptor theory in innate immune activation : studies on the receptors for bacillus Culmet Guillen-cell wall skeleton (BCG-CWS) (review)."Arch.Immunol.Ther.Exp.. (in press). (2001)

[文献書誌] Seya,T et al: "CD46 : membrane cofactor protein of complement and a measles virus receptor (review)."Encyclopedia of Molecular Medicine Ed.by T.E.Creighton.John Wiley & Sons, Inc.New York, NY pp. (in press).. (2001)

[文献書誌] Begum,N.A et al: "Molecular mechanisms of activation of the human innate immune system (review)."Cur.Trends Immunol.. (in press).. (2001)

[文献書誌] Azuma,I.and T.Seya.: "Cell wall skeleton of BCG : application to adjuvant immunotherapy for cancer (review)."Immunopharmacology. (in press).. (2001)

2000 年度実績報告書

瀬谷司大阪府立成人病センター研究所, 第6部・免疫, 部長 (10301805)