title: c-Rel in GVHD biology: a missing link.
abstract: Graft-versus-host disease (GVHD) is a major complication associated with allogeneic bone marrow transplantation (BMT). Recent advances in the treatment of lymphoid malignancies with BMT include exploring mechanisms that can inhibit GVHD while maintaining graft-versus-leukemic (GVL) effects. In this issue of the European Journal of Immunology, Yu et al. [Eur. J. Immunol. 2013.43: 2327-2337] demonstrate efficient separation of GVHD and GVL by abrogating c-Rel in T cells. Intrinsic c-Rel deficiency in T cells resulted in complete protection against GVHD in both major and minor histocompatibility mismatched murine models of BMT. Protection against GVHD was associated with a decreased presence of Th1 and Th17 cells with a concomitant increase in Treg-cell numbers. Interestingly, an intrinsic defect of c-Rel also resulted in decreased expression of the Th1-associated chemokine receptor CXCR3. Finally, the absence of c-Rel maintained GVL effects with significant tumor clearance in murine recipients. These data suggest that specific targeting of the T-cell-specific transcription factor c-Rel can inhibit GVHD while maintaining GVL effects.
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Shoba
authors.initials: S
authors.lastname: Amarnath
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D020569:Proto-Oncogene Proteins c-rel
keywords: GVHD; GVL; Transplantation; c-Rel
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