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

• Project/Area Number: 16616003
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: アレルギー
• Research Institution: Chiba 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: ¥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)
• Keywords: memory 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).

Research Products

• [Journal Article] Crucial role of MLL for the maintenance of memory T helper type 2 cell responses (2006)
  • Author(s): Yamashita, M.
  • Journal Title: Immunity in press
  • Description: 「研究成果報告書概要(和文)」より
• [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
• [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
• [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
• [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
• [Journal Article] Crucial role of MLL for the maintenance of memory T helper type 2 cell responses (2006)
  • Author(s): Yamashita, M.
  • Journal Title: Immunity (in press)
• [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
• [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
• [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
• [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
• [Journal Article] Regulation of Th2 cell differentiation by murine Schnurri-2 (2005)
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Book] The Innate Immune System : Strategies for Disease Control(International Congress Series 1285) (2005)
  • Author(s): Nakayama, T.
  • Total Pages: 216
  • Publisher: Elsevier