Role of glucocorticoid-induced leucine zipper (GILZ) expression by dendritic cells in tolerance induction.

Dendritic cells (DCs) play a crucial role in T cell allorecognition in the context of organ transplantation and allogeneic hematopoietic stem cell transplantation (allo-HSCT). This DC function is believed to be directly involved in allo-HSCT morbidity and mortality. DC functions range from immunoaggressive responses to the promotion of tolerance, reflecting functional plasticity. This unique characteristic offers a rationale to propose generation of tolerogenic DCs as a therapeutic tool for graft-versus-host disease (GVHD). The accumulated preclinical findings support the concept that glucocorticoid-induced leucine zipper (GLIZ) expression redirects mature DC function toward a tolerogenic mode, driving differentiation of antigen-specific regulatory T cells. Taking into account the unique role of DCs within the allo-HSCT context, novel preventive and curative therapeutics for GVHD might be based on the selective induction of GILZ expression in vivo.
(Copyright © 2010 Elsevier Inc. All rights reserved.)