Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Role of glucocorticoid-induced leucine zipper (GILZ) expression by dendritic cells in tolerance induction. 2097 Jun 83

Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft-versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to-dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL-10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL-12p70 production, demonstrating that GILZ is critical for this profile. PUVA-induction of GILZ expression by DC may help explain how ECP suppresses GVHD and OTR. Conversely, those ECP-processed monocytes minimally exposed to PUVA may mediate ECP's immunogenic effects.
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PMID:Activation of GILZ gene by photoactivated 8-methoxypsoralen: potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy. 2421 40