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Research and development for regulating the Th17 responses by utilizing the adjuvant properties of human natural killer T cell subsets.

Research Project

Project/Area Number 20591190
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKansai Medical University

Principal Investigator

UEMURA Yasushi  Kansai Medical University, 腫瘍免疫学部, 主任研究員 (40364781)

Co-Investigator(Renkei-kenkyūsha) SASAKI Yutaka  関西医科大学, 幹細胞生物学分野, 講師 (80425066)
SONODA Yoshiaki  関西医科大学, 幹細胞生物学分野, 教授 (60206688)
MOTOHARU Suzuki  埼玉医科大学, 産婦人科学講座, 助教 (50406443)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords自己免疫疾患 / がん / 免疫 / NKT細胞 / 樹状細胞 / 自己免疫 / 炎症 / 免疫制御 / 免疫学 / 癌
Research Abstract

CD1d-restricted invariant NKT cells play crucial roles of immune responses, infectious diseases and tumor surveillance. However, the mechanisms by which NKT cells exert immune regulatory function remain elusive. In this study, we found that the activation of human NKT cells enhances IL-12p70 while inhibiting the IL-23 production by dendritic cells, in turn down-regulating the IL-17 production by memory CD4+ Th cells. This finding suggests that NKT cells modify the IL-12p70/IL-23 balance to enhance the cell-mediated immunity and suppress the IL-23-dependent inflammatory pathologies.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (49 results)

All 2010 2009 2008 Other

All Journal Article (21 results) (of which Peer Reviewed: 9 results) Presentation (27 results) Remarks (1 results)

  • [Journal Article] In vivo dynamics of human cord blood-derived CD34^- SCID-repopulating cells using intra-bone marrow injection.2010

    • Author(s)
      Kimura T., Matsuoka Y., Murakami M., Kimura T., Takahashi M., Nakamoto T., Yasuda K., Matsui K., Kobayashi K., Imai S., Asano H., Nakatsuka R., Uemura Y., Sasaki Y., Sonoda Y.
    • Journal Title

      Leukemia 24

      Pages: 162-168

    • Related Report
      2010 Final Research Report
  • [Journal Article] 5-Aza-2'-deoxycytidine treatment induces skeletal myogenic differentiation of mouse dental pulp stem cells.2010

    • Author(s)
      Nakatsuka R., Nozaki T., Uemura Y., Matsuoka Y., Sasaki Y., Shinohara, M., Ohura, K., Sonoda Y.
    • Journal Title

      Arch.Oral Biol. 55

      Pages: 350-357

    • Related Report
      2010 Final Research Report
  • [Journal Article] Bisphenol A in combination with TNFα selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity.2010

    • Author(s)
      Guo, H., Liu T-Y., Uemura Y., Jiao. S., Wang, D., Lin, Z., Narita Y., Suzuki M., Hirosawa, M., Ichihara, Y., Ishihara O., Kikuchi H., Sakamoto, Y., Senju, S., Zhang, Q., Ling, F.
    • Journal Title

      Cell.Mol.Immunol. 7

      Pages: 227-234

    • Related Report
      2010 Final Research Report
  • [Journal Article] Development of a High Resolution Purification Method for Precise Functional Characterization of Primitive Human Cord Blood-derived CD34-negative SCID-repopulating Cells2010

    • Author(s)
      Ishii, M., Matsuoka Y., Sasaki Y., Nakatsuka R., Takahashi M., Nakamoto, T., Yasuda, K., Matsui, K., Asano, H., Uemura, Y., Tsuji, T., Fukuhara S., Sonoda Y.
    • Journal Title

      Exp.Hematol. 39

      Pages: 203-213

    • Related Report
      2010 Final Research Report
  • [Journal Article] NKT細胞のアジュバント効果と抗腫瘍免疫応答への応用2010

    • Author(s)
      成田弥生, 鈴木元晴, 劉天懿, 村上真理, 松岡由和, 中塚隆介, 長谷真, 河野比良夫, 佐々木豊, 廣澤成美, 坂本安, 植村靖史, 薗田精昭
    • Journal Title

      Cytometry Research 20(1)

      Pages: 19-25

    • Related Report
      2010 Final Research Report
  • [Journal Article] Development of a High Resolution Purification Method for Precise Functional Characterization of Primitive Human Cord Blood-derived CD34-negative SCID-repopulating Cells2010

    • Author(s)
      Ishii, M.
    • Journal Title

      Exp.Hematol.

      Volume: 39 Pages: 203-213

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 5-Aza-2-deoxycytidine treatment induces skeletal myogenic differentiation of mouse dental pulp stem cells.2010

    • Author(s)
      Nakatsuka, R.
    • Journal Title

      Arch-Oral Biol.

      Volume: 55 Pages: 350-357

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NKT細胞のアジュバント効果と抗腫瘍免疫応答への応用2010

    • Author(s)
      成田弥生
    • Journal Title

      Cytometry Research

      Volume: 20 Pages: 19-25

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo dynamics of human cord blood-derived CD34^- SCID-repopulating cells using intra-bone marrow injection2010

    • Author(s)
      木村貴文
    • Journal Title

      Leukemia 24

      Pages: 162-168

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Marginal expression of CXCR4 on c-kit^+Sca-1^+Lineage^- hematopoietic stem/progenitor cells.2009

    • Author(s)
      Sasaki Y, Matsuoka Y, Hase M, Toyohara T, Murakami M, Takahashi M, Nakatsuka R, Uemura Y, Sonoda Y
    • Journal Title

      Int.J.Hematol. 90

      Pages: 553-560

    • NAID

      10026109792

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Vα24 invariant natural killer T cells.2009

    • Author(s)
      Uemura Y., Liu T-Y. Narita Y., Suzuki M., Nakatsuka R., Araki, T., Matsumoto, M., Iwai L.K., Hirosawa, N., Matsuoka Y., Murakami M., Kimura, T., Hase, M., Kohno, H., Sasaki Y., Ichikawa, Y., Ishihara O., Kikuchi, H., Sakamoto Y., Jiao, S-C., Senju, S., Sonoda Y.
    • Journal Title

      J.Immunol. 183

      Pages: 201-208

    • Related Report
      2010 Final Research Report
  • [Journal Article] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Va24 invariant natural killer T cells2009

    • Author(s)
      植村靖史
    • Journal Title

      Journal of Immunology 183

      Pages: 201-208

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Marginal expression of CXCR4 on c-kit^+Sca-1^+Lineage^- hematopoietic stem/progenitor cells2009

    • Author(s)
      佐々木豊
    • Journal Title

      International Journal of Hematology 90

      Pages: 553-560

    • NAID

      10026109792

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 17-Estradiol (E2) plus TNFα induces a distorted maturation of human monocytes-derived DCs and promotes their capacity to initiate Th2 responses.2008

    • Author(s)
      植村靖史, 劉天懿, 成田弥生, 鈴木元晴, 松下祥
    • Journal Title

      Hum.Immunol. 69

      Pages: 149-157

    • Related Report
      2010 Final Research Report
  • [Journal Article] Role of human non-invariant NKT lymphocytes in the maintenance of type 2T helper environment during pregnancy.2008

    • Author(s)
      Uemura Y., Suzuki M., Liu T-Y., Narita Y., Hirata, S., Ohyama, H., Ishihara O., Matsushita S.
    • Journal Title

      Int.Immunol. 20

      Pages: 405-412

    • NAID

      10021239996

    • Related Report
      2010 Final Research Report
  • [Journal Article] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells.2008

    • Author(s)
      Liu T-Y., Uemura Y., Suzuki, M., Narita Y., Hirata, S., Ohyama, H., 石原理, 松下祥
    • Journal Title

      Eur.J.Immunol. 38(*equal contribution.)

      Pages: 1012-1023

    • Related Report
      2010 Final Research Report
  • [Journal Article] NKT細胞による樹状細胞を介したTヘルパー応答制御2008

    • Author(s)
      植村靖史、劉天懿、鈴木元晴、成田弥生、松下祥
    • Journal Title

      臨床免疫・アレルギー科 49

      Pages: 377-383

    • Related Report
      2010 Final Research Report
  • [Journal Article] 妊娠の維持における脱落膜non-invariantNKT 細胞の役割2008

    • Author(s)
      鈴木元晴、植村靖史、劉天懿、成田弥生、石原理、松下祥
    • Journal Title

      臨床免疫・アレルギー科 49

      Pages: 395-400

    • Related Report
      2010 Final Research Report
  • [Journal Article] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells2008

    • Author(s)
      Yasushi Uemura
    • Journal Title

      European Journal of Immunology 38

      Pages: 1012-1023

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of human non-invariant NKT lymphocytes in the maintenance of tvpe2 T helper environment during pregnancy2008

    • Author(s)
      Yasushi Uemura
    • Journal Title

      International Immunology 20

      Pages: 405-412

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 17β-Estradiol (E2) plus TNFα induces a distorted maturation of human monocytes-derived DCs and promotes their capacity to initiate Th2 responses2008

    • Author(s)
      Yasushi Uemura
    • Journal Title

      Human Immunology 69

      Pages: 149-157

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Vα24 invariant natural killer T cells2010

    • Author(s)
      Y.Uemura, T.Liu, Y.N.Nobori, M.Suzuki, N.Hirosawa, Y.Ichihara, O.Ishihara, H.Kikuchi, Y.Sakamoto, Y.Sonoda, S.Senju
    • Organizer
      14^<th> International Congress of Immunology.
    • Place of Presentation
      Kobe, Japan.
    • Related Report
      2010 Final Research Report
  • [Presentation] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells2010

    • Author(s)
      T.Liu, M. Suzuki, Y.N.Nobori, Y.Guo, N.Hirosawa, Y.Ichihara, Y.Sakamoto, O.Ishihara, H.Kikuchi, S.Senju, Y.Uemura
    • Organizer
      14^<th> International Congress of Immunology.
    • Place of Presentation
      Kobe, Japan.
    • Related Report
      2010 Final Research Report
  • [Presentation] Role of human non-invariant NKT lymphocytes in the maintenance of type 2 T helper environment during pregnancy2010

    • Author(s)
      M.Suzuki, Y.Uemura, T.Liu, Y.N.Nobori, N.Hirosawa, S.Uchino, Y.Ichihara, H.Kikuchi, Y.Sakamoto, S.Senju, O.Ishihara
    • Organizer
      14^<th> International Congress of Immunology.
    • Place of Presentation
      Kobe, Japan.
    • Related Report
      2010 Final Research Report
  • [Presentation] Bisphenol A in combination with TNFα selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity2010

    • Author(s)
      Y.N.Nobori, H.Guo, T.Liu, N.Hirosawa, Y.Uemura, S.Jiao, D.Wang, Z.Lin, M.Suzuki, Y.Ichihara, O.Ishihara, S.Senju, H.Kikuchi, Y.Sakamoto, Y.Sonoda
    • Organizer
      14^<th> International Congress of Immunology.
    • Place of Presentation
      Kobe, Japan.
    • Related Report
      2010 Final Research Report
  • [Presentation] Prospective Isolation and Functional Characterization of Human Bone Marrow-derived Hematopoietic Stem Cell-supportive Mesenchymal Stromal Cells2010

    • Author(s)
      Yoshikazu Matsuoka, Yutaka Sasaki, Masaya Takahashi, Ryusuke Nakatsuka, Yasushi Uemura, Masami Inoue, Hiroyasu Ogawa, Takayuki Takahashi, Jun Ishikawa, Masayuki Hino, Yoshiaki Sonoda
    • Organizer
      52^<st> ASH Annual Meeting.
    • Place of Presentation
      Orlando, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Prospective isolation and functional characterization of human hematopoietic stem cell-supportive mesenchymal stromal cells.2010

    • Author(s)
      松岡由和, 佐々木豊, 高橋昌也, 中塚隆介, 植村靖史, 薗田精昭
    • Organizer
      第8回幹細胞シンポジウム
    • Place of Presentation
      淡路市
    • Related Report
      2010 Final Research Report
  • [Presentation] High resolution purification and functional characterization of primitive human cord blood-derived CD34-negative SRCs2010

    • Author(s)
      佐々木豊, 村上真理, 松岡由和, 高橋昌也, 中塚隆介, 植村靖史, 薗田精昭
    • Organizer
      第8回幹細胞シンポジウム
    • Place of Presentation
      淡路市
    • Related Report
      2010 Final Research Report
  • [Presentation] Yoshiaki Sonoda Prospective isolation of mouse Sca-1^+PDGFRα^+ dental pulp stem cells (DPSCs) existing in the tooth forming niche.2010

    • Author(s)
      中塚隆介, 植村靖史,松岡由和, 佐々木豊
    • Organizer
      第8回幹細胞シンポジウム
    • Place of Presentation
      淡路市
    • Related Report
      2010 Final Research Report
  • [Presentation] HLA-A24 拘束性ピューロマイシン感受性アミノペプチダーゼ特異的CTLのエピトープはオートファジーを介して膵がん細胞に提示される2010

    • Author(s)
      岡村(出町)文子, 鳥養宏基, 赤塚美樹, 近藤紳司, 廣澤友也, 西尾信博, 植村靖史, 葛島清隆
    • Organizer
      第14回日本がん免疫学会総会
    • Place of Presentation
      熊本市
    • Related Report
      2010 Final Research Report
  • [Presentation] c-kit 発現レベルに基づくマウス骨髄造血幹細胞分画の検討2010

    • Author(s)
      佐々木豊, 松岡由和, 中塚隆介, 植村靖史, 薗田精昭
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] 未分化CD34 抗原陰性造血幹細胞の支持能を持つヒト骨髄由来ストローマ細胞の予期的分離とその機能解析2010

    • Author(s)
      松岡由和, 佐々木豊, 高橋昌也, 中塚隆介, 井上雅美, 小川啓恭, 高橋隆幸, 石川淳, 日野雅之, 植村靖史, 薗田精昭
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Va24 invariant natural killer T cells2010

    • Author(s)
      Uemura, Y.
    • Organizer
      14th International Congress of Immunology
    • Place of Presentation
      神戸国際コンベンションセンター(兵庫県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification of functional typl ryanodine receptors in human dendritic cells.2009

    • Author(s)
      Yayoi Narita, Yasushi Uemura, Masanori Tsukamoto, Yasuko Ichihara, Hirosato Kikuchi
    • Organizer
      2009 Annual Meeting of European Malignant Hyperthermia Group.
    • Place of Presentation
      Victoria, Australia.
    • Related Report
      2010 Final Research Report
  • [Presentation] High resolution purification and characterization of human cord blood-derived CD34-negative SCID-repopulating cells with a very immature phenotype.2009

    • Author(s)
      Mari Murakami, Yoshikazu Matsuoka, Ryusuke Nakatsuka, Masaya Takahashi, Tsuyoshi Nakamoto, Katsuhiko Yasuda, Kazuo Matsui, Yasushi Uemura, Yutaka Sasaki, Takashi Tsuji, Shirou Fukuhara, Yoshiaki Sonoda
    • Organizer
      51^<st> ASH Annual Meeting Dec.
    • Place of Presentation
      New Orleans, USA(5-9)
    • Related Report
      2010 Final Research Report
  • [Presentation] In vivo dynamics of human cord blood-derived CD34^-SCID-repopulating cells (SRCs) in comparison to CD34^-CD38^+ SRCs using intra-bone marrow injection.2009

    • Author(s)
      Yoshiaki Sonoda, Takafumi Kimura, Yoshikazu Matsuoka, Mari Murakami, Tsuyoshi Nakamoto, Katsuhiko Yasuda, Ryusuke Matsuoka, Yasushi Uemura, Yutaka Sasaki
    • Organizer
      2009 2^<nd> TERMIS World Congress in conjunction with 2009 Seoul Stem Cell Symposium
    • Place of Presentation
      Republic of Korea
    • Related Report
      2010 Final Research Report
  • [Presentation] 臍帯血由来血管内皮前駆細胞に対するIL-8の作用について2009

    • Author(s)
      木村卓, 松岡由和, 植村靖史, 佐々木豊, 福原資郎, 薗田精昭
    • Organizer
      第31回日本造血細胞移植学会総会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Presentation] CD45陰性歯髄幹細胞の探索と筋系譜細胞への分化転換2009

    • Author(s)
      中塚隆介, 野崎中成, 松岡由和, 菅野渉平, 植村靖史, 佐々木豊, 薗田精昭
    • Organizer
      第8回日本再生医療学会総会
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Prospective isolation and characterization of mouse Sca-1 and PDGFRα double positive dental pulp stem cells2009

    • Author(s)
      中塚隆介, 松岡由和, 植村靖史, 佐々木豊, 薗田精昭
    • Organizer
      第9回日本再生医療学会総会
    • Place of Presentation
      広島
    • Related Report
      2010 Final Research Report
  • [Presentation] Kinetics of CXCR4 expression on murine steady state KSL cells2009

    • Author(s)
      Yutaka Sasaki, Yoshikazu Matsuoka, Takayuki Toyohara, Makoto Hase, Ryusuke Nakatsuka, Yasushi Uemura, Yoshiaki Sonoda
    • Organizer
      第7回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Isolation of mouse dental pulp-derived Sca-1^+PDGFRα^+ tissue-committed stem cells.2009

    • Author(s)
      中塚隆介, 松岡由和, 植村靖史, 佐々木豊, 薗田精昭
    • Organizer
      第7回幹細胞シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Valpha24 invariant NKT cells2009

    • Author(s)
      Motoharu Suzuki, Yasushi Uemura, Yayoi Narita, Tianyi Liu, Narumi Hirisawa, Makoto Hase, Satoru Senju, Yasushi Sakamoto, Yoshiaki Sonoda
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] Modification of IL-12p70 and IL-23 balance in dendritic cells by Valpha24 invariant NKT cells2009

    • Author(s)
      Yasushi Uemura, Tianyi Liu, Yayoi Narita, Motoharu Suzuki, Ryusuke Nakatsuka, Narumi Hirosawa, Yoshikazu Matsuoka, Mari Murakami, Makoto Hase, Hirao Kohno, Yutaka Sasaki, Yasushi Sakamoto, Satoru Senju, Yoshiaki Sonoda
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] ヒト未分化CD34抗原陰性造血幹細胞の純化とその特性解明2009

    • Author(s)
      村上真理, 松岡由和, 中塚隆介, 植村靖史, 佐々木豊, 福原資郎, 薗田精昭
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス骨髄造血幹/前駆細胞は、CXCR4低発現である2009

    • Author(s)
      佐々木豊, 松岡由和, 豊原貴之, 長谷真, 中塚隆介, 植村靖史, 薗田精昭
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス骨髄由来Lineage^-Sca-1^+c-kit^<low/->細胞の造血幹(前駆)細胞特性の解明2009

    • Author(s)
      松岡由和, 佐々木豊, 中塚隆介, 植村靖史, 薗田精昭
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Vα24 invariant NKT cells2009

    • Author(s)
      Tianyi Liu, Yasushi Uemura, Yayoi Narita, Motoharu Suzuki, Satoru Senju, Yoshiaki Sonoda
    • Organizer
      第39回日本免疫学会総会・学術総会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Modification of IL-12p70 and IL-23 balance in dendritic cells by Valpha24 invariant NKT cells2009

    • Author(s)
      植村靖史
    • Organizer
      第71回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2009 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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