2011 Fiscal Year Final Research Report
Synthetic Retinoid Am80 Ameliorates Chronic Graft-Versus-Host Disease by Downregulating Th1 and Th17
| Project/Area Number |
21591244
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Okayama University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 同種造血幹細胞移植 / 移植片対宿主病 |
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| 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.
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