Elucidation of the molecular mechanisms of CD4 T cell-induced osteoblastic hematopoietic niche impairments after bone marrow transplantation
| Project/Area Number |
23790432
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
UEHA Satoshi 東京大学, 大学院・医学系研究科, 助教 (00447385)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 炎症 / 移植免疫 / 造血幹細胞 / GVHD / 骨芽細胞 |
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| Research Abstract |
Using mouse allo-HSCT models, we revealed that fibroblasts/mesenchymal stem cells as well as osteoblasts were damaged early after allo-HSCT, and that the recovery of osteoblasts from X-ray irradiation-mediated damage was impaired in mice with GVHD. The osteoblast impairments were partially dependent on MHC class II on host non-hematopoietic cells, whereas the killing and growth inhibition of osteoblast cell lines required activation of allo-CD4 T cells. Based on gene expression analyses, we identified an osteoblast inhibitory factor, which was specifically expressed in allo-CD4 T cells, as a candidate mediator of osteoblast impairment during BM GVHD. We expect that our results would contribute to the development of early diagnostic markers as well as the preventive and therapeutic strategies against BM GVHD.
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Report
(3 results)
Research Products
(14 results)
