Retinoic acid attenuates acute heart rejection by increasing regulatory T cell and repressing differentiation of Th17 cell in the presence of TGF-[beta]
Summary Retinoic acid (RA), in a transforming growth factor beta (TGF-[beta])-dependent manner, promotes differentiation of regulatory T cells (Tregs) but inhibits the differentiation of Th17 cells in vitro from naive CD4+T cells. In addition, transfer of induced Tregs (iTregs) reduces rejection. We...
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Published in | Transplant international Vol. 23; no. 10; p. 986 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Groningen
Blackwell Publishing Ltd
01.10.2010
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Subjects | |
Online Access | Get full text |
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Summary: | Summary Retinoic acid (RA), in a transforming growth factor beta (TGF-[beta])-dependent manner, promotes differentiation of regulatory T cells (Tregs) but inhibits the differentiation of Th17 cells in vitro from naive CD4+T cells. In addition, transfer of induced Tregs (iTregs) reduces rejection. We therefore examined whether RA could attenuate acute cardiac transplant rejection in vivo in a mouse model by regulating the reciprocal differentiation of Tregs and Th17 cells. The iTregs and naive T cells were respectively transferred into congenic mice. Two weeks later, the percentages of transferred cells and Forkhead box P3 (FoxP3)+ Tregs were measured in spleen. Mice with cardiac transplants were treated with TGF-[beta] alone, RA alone, both or none. The percentage of Tregs or Th17 cells in CD4+T cells, the level of FoxP3 protein or serous interleukin (IL)-17A, or suppressive function of Tregs from recipient mice were assessed. The percentage of Th17 cells and level of serum IL-17A both increased significantly during acute rejection. RA favored differentiation to Tregs over Th17 cells. Unlike naive T cells, only a few transferred iTregs remained after transfer. Treatment with RA plus TGF-[beta] prolonged graft survival, increased the percentage of Tregs, and decreased the percentage of Th17 cells in peripheral T cells. Tregs from all recipients had normal suppressive function. In conclusion, treatment with RA plus TGF-[beta] attenuates acute rejection by promoting the differentiation of Tregs and inhibiting the differentiation of Th17 cells. |
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ISSN: | 0934-0874 1432-2277 |
DOI: | 10.1111/j.1432-2277.2010.01080.x |