Crosstalk between GVHD and fungal infection

• Project/Area Number: 15K15358
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: Teshima Takanori 北海道大学, 医学研究科, 教授 (40284096)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: GVHD / Candida / 肺 / Th17 / Dectin-2 / mannan / 真菌感染 / Mannan / Heat shock protein / 造血幹細胞移植 / 真菌 / カンジダ

Outline of Final Research Achievements

We evaluated mechanistic link between graft-versus-host disease (GVHD) and Candida infection after allogeneic hematopoietic stem cell transplantation (SCT) in mouse models. Injection of alpha-Mannan, a major component of fungal cell wall, or heat-killed Candida albicans accelerated lung GVHD. alpha-Mannan induced donor Th17 differentiation and lung specific chemokine environment in GVHD led to Th17 infiltration to the lung. Such effects of alpha-Mannan on GVHD was dependent on both recipient Dectin-2 and donor IL-17A. These results demonstrate a novel mechanistic link between GVHD and Candida infection following allogeneic SCT.

Research Products

• [Int'l Joint Research] Queensland Institute of Medical Research(Australia)
• [Int'l Joint Research] Queensland Institute of Medical Research(Ａｕｓｔｒａｌｉａ)
• [Journal Article] Graft-versus-host disease targets ovary and causes female infertility in mice. (2017)
  • Author(s): S. Shimoji, D. Hashimoto, H. Tsujigiwa, K. Miyawaki, K. Kato, S. Takahashi, R. Ogasawara, T. Jiromaru, H. Iwasaki, T. Miyamoto, K. Akashi, *T. Teshima
  • Journal Title: Blood Volume: 129 Issue: 9 Pages: 1216-1225
  • DOI: 10.1182/blood-2016-07-728337
  • Peer Reviewed
• [Journal Article] Acute Graft-versus-Host Disease: Novel Biological Insights (2016)
  • Author(s): Teshima T, Reddy P, Zeiser R
  • Journal Title: Biol Blood Marrow Transplant Volume: 22 Pages: 11-16
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice (2015)
  • Author(s): .Uryu H, Hashimoto D, Kato K, Hayase E, Matsuoka S, Ogasawara R, Takahashi S, Maeda Y, Iwasaki H, Miyamoto T, Saijo S, Iwakura Y, Hill GR, Akashi K, Teshima T
  • Journal Title: Blood Volume: 125 Pages: 3014-3023
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Decreased secretion of Paneth cell α-defensin in graft-versus-host disease (2015)
  • Author(s): .Eriguchi Y, Nakamura K, Hashimoto D, Shimoda S, Shimono N, Akashi K, Ayabe T, Teshima T
  • Journal Title: Transpl Infect Dis Volume: 17 Pages: 702-706
  • Peer Reviewed
• [Journal Article] The primacy of IL-6 in IPS? (2015)
  • Author(s): Teshima T
  • Journal Title: Blood Volume: 125 Pages: 2320-2322
  • Peer Reviewed
• [Presentation] Vitamin A-Coupled Liposomes Carrying siRNA Against HSP47 Ameliorate Skin Fibrosis in Chronic Graft-Versus-Host Disease (2016)
  • Author(s): Yamakawa T, Hashimoto D, Hayase E, Takahashi S, Teshima T
  • Organizer: American Society of Hematology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] R-spondin1 promotes Paneth cell growth, maintains intestinal microbial ecology, and ameliorates GVHD (2016)
  • Author(s): Hayase E, Hashimoto D, Nakamura K, Ogura Y, Hayashi T, Kurokawa K, Ayabe T, Teshima T
  • Organizer: The 7th JSH International Symposium
  • Place of Presentation: 兵庫県淡路市淡路夢舞台国際会議場
  • Year and Date: 2016-05-13
  • Int'l Joint Research
• [Presentation] JAK inhibition for GVHD (2016)
  • Author(s): Teshima T
  • Organizer: 42nd EBMT Anuual Meeting
  • Place of Presentation: Valencia, Spain
  • Year and Date: 2016-04-03
  • Int'l Joint Research / Invited
• [Presentation] GVHD組織障害の新たな概念 (2016)
  • Author(s): 豊嶋崇徳
  • Organizer: 第38回 日本造血幹細胞移植学会総会
  • Place of Presentation: 愛知県、名古屋国際会議場、名古屋
  • Year and Date: 2016-03-03
  • Invited
• [Presentation] Emerging concepts on tissue injury in GVHD (2016)
  • Author(s): Teshima T
  • Organizer: BMT Tandem Meetings 2016
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2016-02-17
  • Int'l Joint Research / Invited
• [Presentation] R-spondin1 promotes Paneth cell growth, maintains intestinal microbial ecology, and ameliorates GVHD (2015)
  • Author(s): Hayase E, Hashimoto D, Nakamura K, Ogura Y, Hayashi T, Kurokawa K, Ayabe T, Teshima T
  • Organizer: American Society of Hematology
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-12-04
  • Int'l Joint Research