2003 Fiscal Year Annual Research Report

樹状細胞、NK-T細胞をベースとした感染免疫系賦活と調節

Research Project

Project/Area Number	15019003
Research Institution	Hokkaido University
Principal Investigator	小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)
Co-Investigator(Kenkyū-buntansha)	柳川芳毅北海道大学, 遺伝子病制御研究所, 助手 (20322852)
Keywords	樹状細胞 / NK-T細胞 / 感染免疫 / ケモカイン / 樹状突起 / エンドサイトーシス / アクチンアセンブリー
Research Abstract	感染源に対して有効な免疫応答を誘導・制御することは、感染防御の観点から重要である。これまで、免疫始動と制御で重要な役割を果たす樹状細胞と、NKT細胞の機能修飾の研究を進め、ケモカインのCCL19とCCL21が、樹状細胞の遊走のみならず、形態変化や抗原取り込みに対しても強い活性を持つことを初めて明らかにした(Blood 2002 ; 2003)。従来、成熟型樹状細胞では抗原取り込みが低下すると考えられてきたが、CCL19などによって細菌などの取り込みが著明に促進されたことは、成熟樹状細胞の役割を再認識させる発見と考えられた。今年度はこれらの変化の基礎となる、ケモカイン刺激後の細胞内骨格の変化を解析し、哺乳動物樹状細胞では初めて、アクチンネットワークの構成と、Apr2/3複合体のリクルートを明らかにした。また、成熟樹状細胞の抗原取り込みに関与するシグナル伝達系として、Cdc42とRacが重要であること、遊走にはJNKとRho伝達系が個別に関与することを初めて明らかにした。さらに、樹状細胞の始動する免疫応答の型に影響を与える因子として、TNF-αとLPSの差(Immunology. 2003a),MAPKとIL-12産生の関係(Immunol.Lett. 2003)、抗酸化剤によるCD40発現の特異的低下(Immunology 2003b)、ヒスタミンによる機能制御(Immunolobiol, 2003)、さらにTNF-α刺激後のp38MAPK活性化の役割(Immunology, 2003c)などを明らかにした。 NK-T細胞に関しては、NK-T欠損の新規ミュータントマウスを発見し、原因遺伝子(CD1d)を解明した。また細菌性スーパー抗原に対するNK-T細胞とメインストリームT細胞の反応性の差についても明らかにした(J.Clin.Exp.Hematopathol. in press)。

Research Products

(25 results)

All Other

All Publications (25 results)

[Publications] Zierhut, M.: "Human genome and diseases : Review "Immunology and functional genomics of Behcet's disease.""Cell.Mol.Life Sci.. 60. 1903-1922 (2003)
[Publications] Kikuchi, K.: "Tumour necrosis factor-α but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation."Immunology. 108. 42-49 (2003)
[Publications] Onoe, K.: "Positive and negative selection of T cell repertoires during differentiation in allogeneic bone marrow chimeras."Transplant Immunol.. 12. 79-83 (2003)
[Publications] Shimada, S.: "Expression of allograft inflammatory factor-1 in mouse uterus and poly (I:C)-induced fetal resorption."Am.J.Repro.Immunol.. 50. 104-112 (2003)
[Publications] Shimada, S.: "No difference in natural-killer-T cell population, but Th2/Tc2 predominance in peripheral blood of recurrent aborters."Am.J.Repro.Immunol.. 50. 334-339 (2003)
[Publications] Yanagawa, Y.: "CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities."Blood. 101. 4923-4929 (2003)
[Publications] Tosa, N.: "Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis."Int.Immunol.. 15. 741-749 (2003)
[Publications] Nakayama, K.: "Impaired degradation of IκB and β-catenin as a result of targeted disruption of the βTrCP1 gene."Proc.Natl.Acad.Sci.USA.. 100. 8752-8757 (2003)
[Publications] Kikuchi, K.: "Differential role of mitogen-activated protein kinases in CD40-mediated IL-12 production by immature and mature dendritic cells."Immunol.Lett.. 89. 149-154 (2003)
[Publications] Morohashi, T.: "Allograft inflammatory factor-1 (AIF-1) regulates trinitrobenzene sulfonic asid (TNBS) -induced colitis."Immunology. 110. 112-119 (2003)
[Publications] Pavlinkova, G.: "Effects of histamine on functional maturation of dendritic cells."Immunobiology. 207. 315-325 (2003)
[Publications] Iijima, N.: "Selective regulation of CD40 expression in murine dendritic cells by thiol antioxidants."Immunology. 110. 197-203 (2003)
[Publications] Iijima, N.: "Role of early and late phase activation of p38 MARK induced by TNF-α or 2,4-dinitrobenzene during maturation of dendritic cells."Immunology. 110. 332-328 (2003)
[Publications] Yamada, H.: "Decrease in a specific killer cell immunoglobulin-like receptor on peripheral natural killer cells in women with recurrent miscarriage of unexplained etiology."Am.J.Reprod.Immunol.. 50. 149-154 (2003)
[Publications] Nagashima, T.: "Analysis of T cell responses to a superantigen, staphylococcal enterotoxin B."J.Clin.Exp.Hematopathol.. (in press).
[Publications] Onoe, K.: "T cell differentiation in allogeneic bone marrow chimeras."Cancer Detection and Prevention. (in press).
[Publications] Takagi, D.: "Immuno-regulatory defects of Vα24^+Vβ11^+ NKT cells in development of Wegener's granulomotosis and relapsing polychondritis."Clin.Exp.Immunol.. (in press).
[Publications] 北市伸義: "NK細胞消去による実験的自己免疫性網膜ぶどう膜炎の軽症化"日本眼科学会雑誌. (印刷中).
[Publications] 菊地一博: "TNF-αによって修飾される樹状細胞の分化と機能"臨床免疫. 40. 126-132 (2003)
[Publications] 柳川芳毅: "樹状細胞機能に対するケモカインの効果"臨床免疫. 40. 415-419 (2003)
[Publications] 小野江和則: "医学大辞典"医学書院. 3062 (2003)
[Publications] Onoe, K.: "Immunorogy of Behcet's Disease"Swets & Zeitilinger, Lisse. 120 (2002)
[Publications] 小野江和則: "New Mook眼科,眼の自己免疫疾患"金原出版. 187 (2003)
[Publications] 小野江和則: "肝臓移植の実際"日本医京(印刷中).
[Publications] 岩渕和也, 小野江和則: "モデル動物の作成と維持"エル・アイ・シー(印刷中).

2003 Fiscal Year Annual Research Report

樹状細胞、NK-T細胞をベースとした感染免疫系賦活と調節

Principal Investigator

小野江 和則 北海道大学, 遺伝子病制御研究所, 教授 (40002117)

Research Products

[Publications] Zierhut, M.: "Human genome and diseases : Review "Immunology and functional genomics of Behcet's disease.""Cell.Mol.Life Sci.. 60. 1903-1922 (2003)

[Publications] Kikuchi, K.: "Tumour necrosis factor-α but not lipopolysaccharide enhances preference of murine dendritic cells for Th2 differentiation."Immunology. 108. 42-49 (2003)

[Publications] Onoe, K.: "Positive and negative selection of T cell repertoires during differentiation in allogeneic bone marrow chimeras."Transplant Immunol.. 12. 79-83 (2003)

[Publications] Shimada, S.: "Expression of allograft inflammatory factor-1 in mouse uterus and poly (I:C)-induced fetal resorption."Am.J.Repro.Immunol.. 50. 104-112 (2003)

[Publications] Shimada, S.: "No difference in natural-killer-T cell population, but Th2/Tc2 predominance in peripheral blood of recurrent aborters."Am.J.Repro.Immunol.. 50. 334-339 (2003)

[Publications] Yanagawa, Y.: "CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant up-regulation of Cdc42 and Rac activities."Blood. 101. 4923-4929 (2003)

[Publications] Tosa, N.: "Critical function of T cell death-associated gene 8 in glucocorticoid-induced thymocyte apoptosis."Int.Immunol.. 15. 741-749 (2003)

[Publications] Nakayama, K.: "Impaired degradation of IκB and β-catenin as a result of targeted disruption of the βTrCP1 gene."Proc.Natl.Acad.Sci.USA.. 100. 8752-8757 (2003)

[Publications] Kikuchi, K.: "Differential role of mitogen-activated protein kinases in CD40-mediated IL-12 production by immature and mature dendritic cells."Immunol.Lett.. 89. 149-154 (2003)

[Publications] Morohashi, T.: "Allograft inflammatory factor-1 (AIF-1) regulates trinitrobenzene sulfonic asid (TNBS) -induced colitis."Immunology. 110. 112-119 (2003)

[Publications] Pavlinkova, G.: "Effects of histamine on functional maturation of dendritic cells."Immunobiology. 207. 315-325 (2003)

[Publications] Iijima, N.: "Selective regulation of CD40 expression in murine dendritic cells by thiol antioxidants."Immunology. 110. 197-203 (2003)

[Publications] Iijima, N.: "Role of early and late phase activation of p38 MARK induced by TNF-α or 2,4-dinitrobenzene during maturation of dendritic cells."Immunology. 110. 332-328 (2003)

[Publications] Yamada, H.: "Decrease in a specific killer cell immunoglobulin-like receptor on peripheral natural killer cells in women with recurrent miscarriage of unexplained etiology."Am.J.Reprod.Immunol.. 50. 149-154 (2003)

[Publications] Nagashima, T.: "Analysis of T cell responses to a superantigen, staphylococcal enterotoxin B."J.Clin.Exp.Hematopathol.. (in press).

[Publications] Onoe, K.: "T cell differentiation in allogeneic bone marrow chimeras."Cancer Detection and Prevention. (in press).

[Publications] Takagi, D.: "Immuno-regulatory defects of Vα24^+Vβ11^+ NKT cells in development of Wegener's granulomotosis and relapsing polychondritis."Clin.Exp.Immunol.. (in press).

[Publications] 北市伸義: "NK細胞消去による実験的自己免疫性網膜ぶどう膜炎の軽症化"日本眼科学会雑誌. (印刷中).

[Publications] 菊地一博: "TNF-αによって修飾される樹状細胞の分化と機能"臨床免疫. 40. 126-132 (2003)

[Publications] 柳川芳毅: "樹状細胞機能に対するケモカインの効果"臨床免疫. 40. 415-419 (2003)

[Publications] 小野江和則: "医学大辞典"医学書院. 3062 (2003)

[Publications] Onoe, K.: "Immunorogy of Behcet's Disease"Swets & Zeitilinger, Lisse. 120 (2002)

[Publications] 小野江和則: "New Mook眼科,眼の自己免疫疾患"金原出版. 187 (2003)

[Publications] 小野江和則: "肝臓移植の実際"日本医京(印刷中).

[Publications] 岩渕和也, 小野江和則: "モデル動物の作成と維持"エル・アイ・シー(印刷中).

小野江和則北海道大学, 遺伝子病制御研究所, 教授 (40002117)