Mechanisms for the attenuated GVHD by blocking IL-21

• Project/Area Number: 21591247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: OZAKI Katsutoshi 自治医科大学, 医学部, 講師 (10286453)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 血液免疫学 / IL-21 / GVHD / 制御性T細胞 / サイトカイン / 移植後合併症 / Th1 / Th2

Research Abstract

We have shown that splenocytes from IL-21R-deficient mice ameliorates GVHD as compared to that from wild-type mice and that a decoy receptor for IL-21 attenuates GVHD. This time, we aimed to investigate the mechanisms for the attenuated GVHD by blocking IL-21.We found that the production of cytokines was impaired in effector T cells and an increase of Treg cells in spleen. A depletion of Treg cells by anti-CD25 antibody did not change the attenuation of GVHD by blocking IL-21, suggesting that the cause of attenuation of GVHD could be the loss of functional effector cells rather than the increase of Treg cells.

Research Products

• [Journal Article] Mesenchymal s tem cells inhibit Th17 but not regula tory T cell differentiation (2011)
  • Author(s): Tatara, R., Ozaki, K., Kikuchi Y., Ha tanaka, K., Oh, I., Meguro, A., Matsu, H., Sato, K. Ozawa, K
  • Journal Title: Cytotherapy Volume: 13(6) Pages: 686-694
• [Journal Article] Lack of IL-21 signal attenu ates graft-versus-leukemia effect in the absence of CD8 T-cells (2011)
  • Author(s): Meguro A, Ozaki K, Hatanaka K, Oh I, Sudo K, Ohmori T, Matsu H, Tatara R, Sato K, Sakata Y, Nakae S, Leonard WJ, Ozawa K
  • Journal Title: Bone Marrow Transplant Volume: 46(12) Pages: 1557-1565
• [Journal Article] Regulato ry T cells and IL-17-producing cells in graft-versus-host disease (2011)
  • Author(s): Teshima T, Maeda Y, Ozaki K
  • Journal Title: Immunot herapy Volume: 3(7) Pages: 833-52
• [Journal Article] Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells (2011)
  • Author(s): Meguro A, Ozaki K, Hatanaka K, Oh I, Sudo K, Ohmori T, Matsu H, Tatara., Sato K, Sakata Y, Nakae S, Leonard W J, and Ozawa K
  • Journal Title: Bone Marrow Transplant Volume: 46巻 Issue: 12 Pages: 1557-1565
  • DOI: 10.1038/bmt.2010.342
  • Peer Reviewed
• [Journal Article] Mesenchymal stem cells inhibit Th17 but not regulatory T cell differentiation (2011)
  • Author(s): Tatara, R
  • Journal Title: Cytotherapy Volume: 13(6) Pages: 686-694
  • Peer Reviewed
• [Journal Article] IL-21 is critical for graft-versus-host disease in a mouse model (2010)
  • Author(s): Meguro A, Ozaki K, Oh I, Hatanaka K, Matsu H, Tatara R, Sato K, Leonard WJ, Ozawa K
  • Journal Title: Bone Marrow Transplant Volume: 45(4) Pages: 723-9
• [Journal Article] Altered effec tor CD4+T cell function in IL-21R-/-CD4+T cell-mediated graft-versus-ho st disease (2010)
  • Author(s): Oh I, Ozaki K, Meguro A, Hatanaka K, Kadowaki M, Matsu H, Tatara R, Sato K, Iwakura Y, Nakae S, Sudo K, Teshima T, Leonard WJ, Ozawa K
  • Journal Title: J Immunol Volume: 185(3) Pages: 1920-1926
• [Journal Article] IL-21 is critical for graft-versus-host disease in a mouse model. (2010)
  • Author(s): Meguro A
  • Journal Title: Bone Marrow Transplant. Volume: 45 Pages: 723-9
  • Peer Reviewed
• [Journal Article] Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft-versus-host disease. (2010)
  • Author(s): Oh I
  • Journal Title: J Immunol. Volume: 185 Pages: 1920-6
  • Peer Reviewed
• [Journal Article] IL-21 is critical for GVHD in a mouse mdel (2010)
  • Author(s): A Meguro
  • Journal Title: Bone Marrow Transplantation (in press)
  • Peer Reviewed
• [Journal Article] A Lower Starting Dose of Eltrombo pag is Efficacious in Japanese Patien ts with Previously Treated Chronic Im mune Thrombocytopenia(ITP)
  • Author(s): Tomiyama Y, Miyakawa Y, Okamato S, Ka tsutani S, Kimura A, Okoshi Y, Ninomi ya H, Kosugi H, Nomura S, Ozaki K, Ik eda Y, Hattori T, Katsura K, Kanakura Y
  • Journal Title: J. Throm b. & Hemost Volume: (in press)
• [Journal Article] Mesenchymal stem cells inhibit Th17 but not regulatory T cell differentiation.
  • Author(s): Tatara R
  • Journal Title: Cytotherapy Volume: (In Press)
  • Peer Reviewed
• [Journal Article] Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells.
  • Author(s): Meguro A
  • Journal Title: Bone Marrow Transplant. Volume: (In Press)
  • Peer Reviewed
• [Presentation] Stat3 is critical for GVHD (2011)
  • Author(s): 尾崎勝俊
  • Organizer: 第52回米国血液学会
  • Place of Presentation: San Diego
  • Year and Date: 2011-12-10
• [Presentation] Stat3 activation in donor CD4 T-cells is critical for acute GVHD (2011)
  • Author(s): Ozaki K, Matsu H, Hatanaka K, Meguro A, Oh I, Tatara R, Suzuki T, Mori M, Muroi K, Nagai T, Ozawa K
  • Organizer: 2011 Annual Meeting of ASH at San Diego
• [Presentation] Mesenchymal stem cell mediated suppression of Th17 differentiation through PGE2 and IDO production (2010)
  • Author(s): Tatara R, Ozaki K, Kikuchi Y, Hatanaka K, Oh I, Meguro A, Matsu H, Sato K, Nagai T, Muroi K, Ozawa K
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
• [Presentation] IL-21のシグナル抑制とgraft-versus-leukemia効果 (2010)
  • Author(s): 目黒明子、尾崎勝俊、畑中恵子、翁家国、松春子、多々良礼音、佐藤一也、大嶺謙、鈴木隆浩、森政樹、永井正、室井一男、須藤カツ子、中江進、小澤敬也
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
• [Presentation] 移植片対宿主病におけるSTAT3の役割に関する発生工学的手法を用いた検討 (2010)
  • Author(s): 松春子、尾崎勝俊、畑中恵子、多々良礼音、目黒明子、翁家国、佐藤一也、鈴木隆浩、森政樹、永井正、室井一男、永井正、植松智、審良静男、小澤敬也
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells. (2010)
  • Author(s): Ozaki K
  • Organizer: 52th ASH Annual Meeting
  • Place of Presentation: Orlando, FL, USA
• [Presentation] Mesenchymal stem cell mediated suppression of Th17 differentiation through PGE2 and IDO production. (2010)
  • Author(s): Tatara, R
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] IL-21のシグナル抑制とgraft-versus-leukemia効果 (2010)
  • Author(s): 目黒明子
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] 移植片対宿主病におけるSTAT3の役割に関する発生工学的手法を用いた検討 (2010)
  • Author(s): 松春子
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Mesenchymal Stem Cells Inhibit Th17 Differentiation through PGE2 Production (2009)
  • Author(s): 多々良礼音
  • Organizer: 第51回米国血液学会総会
  • Place of Presentation: ERENEST N.MORIAL CONVEN TION CENTER NEW ORLEANS
  • Year and Date: 2009-12-03
• [Presentation] CD4陽性T細胞の移植によって誘導されるGVHDとIL-21の重要性 (2009)
  • Author(s): 翁家国
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-10-25
• [Presentation] 間葉系幹細胞(MSC)がTh17、Treg分化に及ぼす影響 (2009)
  • Author(s): 多々良礼音
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-10-25
• [Presentation] Blocking of IL-21 signal attenuates graft-versus-host disease but not graft-versus-leukemia effect in a mouse model (2009)
  • Author(s): Meguro A, Ozaki K, Oh I, Matsu H, Hatanaka K, Sato K, Tatara R, Suzuki T, Mori M, Nagai T, Muroi K, Ozawa K
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 間葉系幹細胞がTh17、Treg分化に及ぼす影響 (2009)
  • Author(s): 多々良礼音, 尾崎勝俊, 畑中恵子, 翁家国, 松春子, 目黒明子, 佐藤一也, 永井正, 室井一男, 小澤敬也
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] CD4陽性T細胞の移植によって誘導されるGVHDとIL-21の重要性 (2009)
  • Author(s): 翁家国, 尾崎勝俊, 目黒明子, 畑中恵子, 多々良礼音, 松春子, 佐藤一也, 永井正, 室井一男, 小澤敬也
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Mesenchymal stem cells inhibit Th17 differentiation through PGE2 production (2009)
  • Author(s): Tatara R, Ozaki K, Oh I, Hatanaka K, Meguro A, Matsu H, Sato K, Nagai T, Muroi K, Ozawa K
  • Organizer: 2009 Annual Meeting of ASH at New Orleans
• [Remarks]
  • URL: http://www.jichi.ac.jp/usr/hema/index.html