Attenuation of acute graft-versus-host disease in the absence of the transcription factor RORγt

LeShara M. Fulton, Michael J. Carlson, James M. Coghill, Laura E. Ott, Michelle L. West, Angela Panoskaltsis-Mortari, Dan R. Littman, Bruce R. Blazar, Jonathan S. Serody

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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)γt. 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 RORγt. 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.

Original languageEnglish (US)
Pages (from-to)1765-1772
Number of pages8
JournalJournal of Immunology
Volume189
Issue number4
DOIs
StatePublished - Aug 15 2012

Bibliographical note

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

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