| First Author | Fulton LM | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 1765-72 |
| PubMed ID | 22778391 | Mgi Jnum | J:189760 |
| Mgi Id | MGI:5446966 | Doi | 10.4049/jimmunol.1200858 |
| Citation | Fulton LM, et al. (2012) Attenuation of acute graft-versus-host disease in the absence of the transcription factor RORgammat. J Immunol 189(4):1765-72 |
| abstractText | Graft-versus-host disease (GVHD) remains the most significant complication after allogeneic stem cell transplantation. Previously, acute GVHD had been considered to be mediated predominantly by Th1-polarized T cells. Recently, investigators have identified a second proinflammatory lineage of T cells termed Th17 that is critically dependent on the transcription factor retinoic acid-related orphan receptor (ROR)gammat. In this study, we have evaluated the role of Th17 cells in murine acute GVHD by infusing donor T cells lacking RORC and as a consequence the isoform RORgammat. Recipients given donor CD4(+) and CD8(+) T cells lacking RORC had significantly attenuated acute GVHD and markedly decreased tissue pathology in the colon, liver, and lung. Using a clinically relevant haploidentical murine transplantation model, we showed that RORC(-/-) CD4(+) T cells alone diminished the severity and lethality of acute GVHD. This was not found when CD4(+) T cells from RORC(-/-) mice were given to completely mismatched BALB/c mice, and it was correlated with absolute differences in the generation of TNF in the colon after transplant. Thus, CD4(+) T cell expression of RORC is important in the pathogenesis of acute GVHD. |
