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Research on the regulatory mechanisms of allergic inflammatory deseases by memory Th2 cells.

Research Project

Project/Area Number 16616003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field アレルギー
Research InstitutionChiba University

Principal Investigator

YAMASHITA Masakatsu  Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (00311605)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsmemory Th2 cell / effector Th2 cell / allergic inflammation / GATA3 / MLL / Bmil / Gfi1 / 好酸球 / IgE / Gfi-1
Research Abstract

One of the difficulties in memory Th2 cell study is limited numbers of antigen-specific memory Th2 cell in vivo. We developed an adoptive transfer technique for the generation of antigen-specific memory Th2 cell in vivo. In brief, CD4 T cells from OVA-specific TCRαβ transgenic mice were stimulated with OVA plus APC under Th2-conditions for 6 days in vitro. Then the generated effector Th2 cells were transferred intravenously into recipient mice. Five weeks after transfer, the large numbers of memory Th2 cells could recover from spleen of recipient mice. In the study, we used this technique and assessed the regulatory mechanisms of allergic inflammatory diseases by memory Th2 cells, especially focused on following two points. First, we tried to identify the transcription factors that control memory Th2 cell differentiation. Second, we determined physiological functions of identified factors in allergic inflammatory diseases using allergic airway inflammation model.
The following results could be achieved for this research on two years.
(1)GATA3 is required for the maintenance of histone modification at the Th2 cytokine gene loci in memory Th2 cells (Yamashita et al. J.Biol.Chem. 279 : 26983,2004), whereas IL-4 is not (Yamashita et al. J.Biol.Chem. 279 : 39454,2004).
(2)MLL is crucial for the maintenance of memory Th2 cell responses (Yamashita et al. Immunity. in press). Bmil (Polycomb group gene) is required in the survival of memory Th2 cells (Yamashita et al. In preparation).

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (33 results)

All 2006 2005 2004 Other

All Journal Article (31 results) Book (2 results)

  • [Journal Article] Crucial role of MLL for the maintenance of memory T helper type 2 cell responses2006

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

      Immunity in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of allergic airway inflammation through Toll lke receptor 4-mediated modification of mast cell function.2006

    • Author(s)
      Nigo, I. Y.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 103・7

      Pages: 2286-2291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired GATA3-dependent chromatin remodeling and Th2 cell differentiation leading to attenuated allergic airway inflammation in aging mice.2006

    • Author(s)
      Hasegawa, A.
    • Journal Title

      J. Immunol. 176・4

      Pages: 2546-2554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of allergic airway inflammation through Toll like receptor 4-mediated modification of mast cell function.2006

    • Author(s)
      Nigo, I.Y., Yamashita, M., Hirahara, K., Shinnakasu, R., Inami, M., Kimura, M., Hasegawa, A., Kohno, Y., Nakayama, T.
    • Journal Title

      Proc.Natl.Acad.Sci. USA. 103

      Pages: 2286-2291

    • NAID

      40015396097

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Impaired GATA3-dependent chromatin remodeling and Th2 cell differentiation leading to attenuated allergic airway inflammation in aging mice.2006

    • Author(s)
      Hasegawa, A, Miki, T., Hosokawa, H., Hossain, M.B., Shimizu, C., Hashimoto, K., Kimura, Y.M., Yamashita, M., Nakayama, T.
    • Journal Title

      J.Immunol. 176

      Pages: 2546-2554

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Crucial role of MLL for the maintenance of memory T helper type 2 cell responses2006

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

      Immunity (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of allergic airway inflammation through Toll like receptor 4-mediated modification of mast cell function.2006

    • Author(s)
      Nigo, I.Y.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 103・7

      Pages: 2286-2291

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Impaired GATA3-dependent chromatin remodeling and Th2 cell differentiation leading to attenuated allergic airway inflammation in aging mice.2006

    • Author(s)
      Hasegawa, A.
    • Journal Title

      J.Immunol. 176・4

      Pages: 2546-2554

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ras-ERK MARK cascade regulates GATA3 stability and Th2 differentiation through ubiqutin-proteasome pathway.2005

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

      J. Biol. Chem. 280・33

      Pages: 29409-29419

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prolonged skin allograft survival by IL-10 gene-introduced CD4 T cell administration.2005

    • Author(s)
      Miyamoto, T.
    • Journal Title

      Int. Immunol. 17・6

      Pages: 759-768

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Th2 cell differentiation by murine Schnurri-22005

    • Author(s)
      Kimura, Y.
    • Journal Title

      J. Exp. Med. 201・3

      Pages: 397-408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through ubiquitin-proteasome pathway.2005

    • Author(s)
      Yamashita, M., Shinnakasu, R., Asou, H., Kimura, M., Hasegawa, A., Hashimoto, K., Hatano, N., Ogata, M., Nakayama, T.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 29409-29419

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Prolonged skin allograft survival by IL-10 gene-introduced CD4 T cell administration.2005

    • Author(s)
      Miyamoto, T., Kaneko, T., Yamashita, M., Tenda, Y., Inami, M., Suzuki, A., Ishii, S., Kimura, M., Hashimoto, K., Shimada, H., Yahata, H., Ochiai, T., Saito, I., DeGregori, J., Nakayama, T.
    • Journal Title

      Int.Immunol. 17

      Pages: 759-768

    • NAID

      10019358742

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulation of Th2 cell differentiation by murine Schnurri-2.2005

    • Author(s)
      Kimura, Y.M., Hosokawa, H., Yamashita, M., Watarai, H., Hasegawa, A., Iwamura, C., Taniguchi, M., Takagi, T., Ishii, S., Nakayama, T.
    • Journal Title

      J.Exp.Med. 201

      Pages: 397-408

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chromatin remodeling of the Th2 cytokine gene loci.2005

    • Author(s)
      Nakayama, T., Yamashita, M., Kimura, M., Hasegawa, A., Omori, M., Inami, M., Motohashi, S., Kitajima, M., Hashimoto, K., Hosokawa, H., Shinnakasu, R.
    • Journal Title

      The Innate Immune System : Strategies for Disease Control (International Congress Series 1285)(Elsevier)

      Pages: 216-216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ras-ERK MAPK cascade regulates GATA3 stability and Th2 differentiation through ubiquitin-proteasome pathway.2005

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

      J.Biol.Chem. 280・33

      Pages: 29409-29419

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prolonged skin allograft survival by IL-10 gene-introduced CD4 T cell administration.2005

    • Author(s)
      Miyamoto, T.
    • Journal Title

      Int.Immunol. 17・6

      Pages: 759-768

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of Th2 differentiation by murine Schnurri-2.2005

    • Author(s)
      Kimura, M.Y.
    • Journal Title

      J.Exp.Med. 201

      Pages: 397-408

    • Related Report
      2004 Annual Research Report
  • [Journal Article] STAT6-dependent differentiation and production of IL-5 and IL-13 in murine NK2 cells.2004

    • Author(s)
      Katsumoto, T.
    • Journal Title

      J. Immunol 173・8

      Pages: 4967-4975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interleukin (IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells.2004

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

      J. Biol. Chem 279・38

      Pages: 39454-39464

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Essential role of GATA3 for the maintenance Type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci.2004

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

      J. Biol. Chem 279・26

      Pages: 26983-26990

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CD28 costimulation controls histone hyperacetylation of the IL-5 gene locus in developing Th2 cells.2004

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

      J. Biol. Chem 279・22

      Pages: 23123-23133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] STAT6-dependent differentiation and production of IL-5 and IL-13 in murine NK2 cells.2004

    • Author(s)
      Katsumoto, T., Kimura, M., Yamashita, M., Hosokawa, H., Hashimoto, K., Hasegawa, A., Omori, M., Miyamoto, T., Taniguchi, M., Nakayama, T.
    • Journal Title

      J.Immunol. 173

      Pages: 4967-4975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interleukin (IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells.2004

    • Author(s)
      Yamashita, M., Shinnakasu, R., Nigo, Y., Kimura, M., Hasegawa, A., Taniguchi, M., Nakayama, T.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 39454-39464

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Essential role of GATA3 for the maintenance of Type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci.2004

    • Author(s)
      Yamashita, M., Ukai-Tadenuma, M., Miyamoto, T., Sugaya, K., Hosokawa, H., Hasegawa, A., Kimura, M., Taniguchi, M., DeGregori, J., Nakayama, T.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 26983-26990

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CD28 costimulation controls histone hyperacetylation of the IL-5 gene locus in developing Th2 cells.2004

    • Author(s)
      Inami, M., Yamashita, M., Tenda, Y., Hasegawa, A., Kimura, M., Hashimoto, K., Seki, N., Taniguchi, M., Nakayama, T.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 23123-23133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] STAT6-dependent differentiation and production of IL-5 and IL-13 imurine NK2 cells.2004

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

      J.Immunol 173

      Pages: 4967-4975

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interleukin(IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells.2004

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

      J.Biol.Chem. 279

      Pages: 39454-39464

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Essential role of GATA3 for the maintenance of Th2 cytokine production and chromatin remodeling at the Th2 cytokine gene loci.2004

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

      J.Biol.Chem. 279

      Pages: 26983-26990

    • Related Report
      2004 Annual Research Report
  • [Journal Article] CD28 costimulation controls histone hyperacetylation of the interlelikin-5 gene locus in developing Tb2 cells.2004

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

      J.Biol.Chem. 279

      Pages: 23123-23133

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Crucial role of MLL for the maintenance of memory T helper type 2 cell responses.

    • Author(s)
      Yamashita, M., Hirahara, K., Shinnakasu, R., Hosokawa, H., Norikane, S., Kimura, Y.M., Hasegawa, A., Nakayama, T.
    • Journal Title

      Immunity (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The Innate Immune System : Strategies for Disease Control (International Congress Series 1285)2005

    • Author(s)
      Nakayama, T.
    • Total Pages
      216
    • Publisher
      Elsevier
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The Innate Immune System : Strategies for Disease Control(International Congress Series 1285)2005

    • Author(s)
      Nakayama, T.
    • Total Pages
      216
    • Publisher
      Elsevier
    • Related Report
      2005 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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