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- W2023485090 abstract "Halofuginone, isolated from Dichroa febreifuga, is a potent inhibitor of skin collagen in chronic graft-versus-host disease (GVHD). To evaluate the effect of halofuginone on the development of cutaneous GVHD, we developed a murine model based on BALB/c (H-2d) as recipients with transplantation of C57BL/6(H-2b) bone marrow plus splenocytes. Halofuginone or its vehicle dimethyl sulfoxide (DMSO) was given introperitoneally at a dose of 5 ug/mouse daily from one day before transplantation until 20 days post-transplantation. Halofuginone-treated recipients showed only very mild appearance of cutaneous GVHD, whereas DMSO-treated recipients rapidly showed manifestation of severe cutaneous GVHD, indicating a protective effect of halofuginone in cutaneous GVHD. After injected with halofuginone, we observed a decrease in the number of CD4+ interleukin (IL)-17+ cells and a parallel increase in that of CD4+ interferon (IFN)-gamma+ cells in peripheral blood. This shift between CD4+ IL-17+ cells and CD4+ IFN-gamma+ cells developed through modulation of cytokine profile indicated by a marked increase in the levels of IFN-gamma, tumor necrosis factor (TNF)-alpha, and IL-6. The level of IL-10 was not changed obviously. Mechanistically, we demonstrate that severe tissue damage was associated with the production of IL-17 and expansion of CD4+IL-17+ cells during this disorder. Specific inhibition of Th17 differentiation by halofuginone reduced disease severity. Our results indicate a significant role of halofuginone in suppressing cutaneous GVHD, apparently through effect on inhibition of Th17 cells differentiation." @default.
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- W2023485090 date "2012-09-01" @default.
- W2023485090 modified "2023-09-26" @default.
- W2023485090 title "Halofugine prevents cutaneous graft versus host disease by suppression of Th17 differentiation" @default.
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- W2023485090 doi "https://doi.org/10.1179/1607845412y.0000000016" @default.
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