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Publication : c-Rel is an essential transcription factor for the development of acute graft-versus-host disease in mice.

First Author  Yu Y Year  2013
Journal  Eur J Immunol Volume  43
Issue  9 Pages  2327-37
PubMed ID  23716202 Mgi Jnum  J:201268
Mgi Id  MGI:5512913 Doi  10.1002/eji.201243282
Citation  Yu Y, et al. (2013) c-Rel is an essential transcription factor for the development of acute graft-versus-host disease in mice. Eur J Immunol 43(9):2327-37
abstractText  Transcription factors of the Rel/NF-kappaB family are known to play different roles in immunity and inflammation, although the putative role of c-Rel in transplant tolerance and graft-versus-host disease (GVHD) remains elusive. We report here that T cells deficient for c-Rel have a dramatically reduced ability to cause acute GVHD after allogeneic bone marrow transplantation using major and minor histocompatibility mismatched murine models. In the study to understand the underlying mechanisms, we found that c-Rel(-/-) T cells had a reduced ability to expand in lymphoid organs and to infiltrate in GVHD target organs in allogeneic recipients. c-Rel(-/-) T cells were defective in the differentiation into Th1 cells after encountering alloantigens, but were enhanced in the differentiation toward Foxp3(+) regulatory T (Treg) cells. Furthermore, c-Rel(-/-) T cells had largely preserved activity to mediate graft-versus-leukemia response. Taken together, our findings indicate that c-Rel plays an essential role in T cells in the induction of acute GVHD, and suggest that c-Rel can be a potential target for therapeutic intervention in allogeneic hematopoietic cell transplantation in the clinic.
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