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

• Project/Area Number: 20591190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kansai 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: ¥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.

Research Products

• [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
• [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
• [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
• [Journal Article] Development of a High Resolution Purification Method for Precise Functional Characterization of Primitive Human Cord Blood-derived CD34-negative SCID-repopulating Cells (2010)
  • 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
• [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
• [Journal Article] Development of a High Resolution Purification Method for Precise Functional Characterization of Primitive Human Cord Blood-derived CD34-negative SCID-repopulating Cells (2010)
  • Author(s): Ishii, M.
  • Journal Title: Exp.Hematol. Volume: 39 Pages: 203-213
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] In vivo dynamics of human cord blood-derived CD34^- SCID-repopulating cells using intra-bone marrow injection (2010)
  • Author(s): 木村貴文
  • Journal Title: Leukemia 24 Pages: 162-168
  • 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
• [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
• [Journal Article] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Va24 invariant natural killer T cells (2009)
  • Author(s): 植村靖史
  • Journal Title: Journal of Immunology 183 Pages: 201-208
  • Peer Reviewed
• [Journal Article] Marginal expression of CXCR4 on c-kit^+Sca-1^+Lineage^- hematopoietic stem/progenitor cells (2009)
  • Author(s): 佐々木豊
  • Journal Title: International Journal of Hematology 90 Pages: 553-560
  • NAID: 10026109792
  • 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
• [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
• [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
• [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
• [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
• [Journal Article] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells (2008)
  • Author(s): Yasushi Uemura
  • Journal Title: European Journal of Immunology 38 Pages: 1012-1023
  • Peer Reviewed
• [Journal Article] Role of human non-invariant NKT lymphocytes in the maintenance of tvpe2 T helper environment during pregnancy (2008)
  • Author(s): Yasushi Uemura
  • Journal Title: International Immunology 20 Pages: 405-412
  • 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 responses (2008)
  • Author(s): Yasushi Uemura
  • Journal Title: Human Immunology 69 Pages: 149-157
  • 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 cells (2010)
  • 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.
• [Presentation] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells (2010)
  • 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.
• [Presentation] Role of human non-invariant NKT lymphocytes in the maintenance of type 2 T helper environment during pregnancy (2010)
  • 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.
• [Presentation] Bisphenol A in combination with TNFα selectively induces Th2 cell-promoting dendritic cells in vitro with an estrogen-like activity (2010)
  • 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.
• [Presentation] Prospective Isolation and Functional Characterization of Human Bone Marrow-derived Hematopoietic Stem Cell-supportive Mesenchymal Stromal Cells (2010)
  • 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
• [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
• [Presentation] High resolution purification and functional characterization of primitive human cord blood-derived CD34-negative SRCs (2010)
  • 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
• [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
• [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
• [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
• [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
• [Presentation] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Va24 invariant natural killer T cells (2010)
  • 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)
• [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.
• [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)
• [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
• [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
• [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
• [Presentation] Prospective isolation and characterization of mouse Sca-1 and PDGFRα double positive dental pulp 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9回日本再生医療学会総会
  • Place of Presentation: 広島
• [Presentation] Kinetics of CXCR4 expression on murine steady state KSL cells (2009)
  • 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
• [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
• [Presentation] Modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Valpha24 invariant NKT cells (2009)
  • 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
• [Presentation] Modification of IL-12p70 and IL-23 balance in dendritic cells by Valpha24 invariant NKT cells (2009)
  • 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
• [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
• [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
• [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
• [Presentation] Cytokine-dependent modification of IL-12p70 and IL-23 balance in dendritic cells by ligand activation of Vα24 invariant NKT cells (2009)
  • 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
• [Presentation] Modification of IL-12p70 and IL-23 balance in dendritic cells by Valpha24 invariant NKT cells (2009)
  • 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)
• [Remarks] ホームページ等