Synthetic Retinoid Am80 Ameliorates Chronic Graft-Versus-Host Disease by Downregulating Th1 and Th17

• Project/Area Number: 21591244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Okayama University
• Principal Investigator: MAEDA Yoshinobu 岡山大学, 岡山大学病院, 助教 (60403474)
• Co-Investigator(Kenkyū-buntansha): 谷本 光音 岡山大学, 大学院・医歯薬学総合研究科, 教授 (10240805)
• Co-Investigator(Renkei-kenkyūsha): TANIMOTO Mitsune 岡山大学, 大学院・医歯薬学総合研究科, 教授 (10240805)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 同種造血幹細胞移植 / 移植片対宿主病 / 慢性GVHD / レチノイド

Research Abstract

Chronic GVHD(cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-βexpression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD.

Research Products

• [Journal Article] Synthetic Retinoid Am80 Ameliorates Chronic Graft-Versus-Host Disease by Downregulating Th1 and Th17 (2012)
  • Author(s): Nishimori H, Maeda Y, et al
  • Journal Title: Blood Volume: 119(1) Pages: 285-95
  • NAID: 130004903194
  • Peer Reviewed
• [Journal Article] Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice. (2010)
  • Author(s): Asakura S, Hashimoto D, Takashima S, Sugiyama H, Maeda Y, Akashi K, Tanimoto M, Teshima T.
  • Journal Title: J Clin Invest. Volume: 120 Pages: 2370-2378
  • NAID: 130004505744
  • Peer Reviewed
• [Presentation] Donor Th17 and Th1 Contribute to Chronic Graft-Versus-Host Disease (2010)
  • Author(s): Nishimori H, Maeda Y, et al.
  • Organizer: ASH Annual Meeting Orland
  • Place of Presentation: USA
  • Year and Date: 2010-12-06
• [Presentation] Donor Th17 and Th1 Contribute to Chronic Graft-Versus-Host Disease (2010)
  • Author(s): H Nishimori, R Sugiyama, K Kobayashi, Y Yamasuji, S Kadohisa, K Takeuchi, Y Iwakura, M Tanimoto, Y Maeda
  • Organizer: アメリカ血液学会
  • Place of Presentation: フロリダ
  • Year and Date: 2010-12-06
• [Presentation] 合成レチノイドAm80によるTh1/Th17を介した慢性GVHD制御 (2010)
  • Author(s): 西森久和、前田嘉信, 他8名
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 静岡
  • Year and Date: 2010-02-19