Inhibition of nuclear factor-kappa B enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis

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dc.contributor.authorIruretagoyena, Mirentxu I.
dc.contributor.authorSepulveda, Sofia E.
dc.contributor.authorLezana, J. Pablo
dc.contributor.authorHermoso, Marcela
dc.contributor.authorBronfman, Miguel
dc.contributor.authorGutierrez, Miguel A.
dc.contributor.authorJacobelli, Sergio H.
dc.contributor.authorKalergis, Alexis M.
dc.date.accessioned2024-01-10T13:49:31Z
dc.date.available2024-01-10T13:49:31Z
dc.date.issued2006
dc.description.abstractAutoimmune disorders develop as a result of deregulated immune responses that target self-antigens and cause destruction of healthy host tissues. Because dendritic cells (DCs) play an important role in the maintenance of peripheral immune tolerance, we are interested in identifying means of enhancing their therapeutic potential in autoimmune diseases. It is thought that during steady state, DCs are able to anergize potentially harmful T cells bearing T cell receptors that recognize self-peptide-major histocompatibility complexes. The tolerogenic capacity of DCs requires an immature phenotype, which is characterized by a reduced expression of costimulatory molecules. On the contrary, activation of antigen-specific naive T cells is enhanced by DC maturation, a process that involves expression of genes controlled by the transcription factor nuclear factor (NF)-kappa B. We evaluated the capacity of drugs that inhibit NF-kappa B to enhance the tolerogenic properties of immature DCs in the experimental autoimmune encephalomyelitis (EAE) model. We show that andrographolide, a bicyclic diterpenoid lactone, and rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, were able to interfere with NF-kappa B activation in murine DCs. As a result, treated DCs showed impaired maturation and a reduced capacity to activate antigen-specific T cells. Furthermore, NF-kappa B-blocked DCs had an enhanced tolerogenic capacity and were able to prevent EAE development in mice. The tolerogenic feature was specific for myelin antigens and involved the expansion of regulatory T cells. These data suggest that NF-kappa B blockade is a potential pharmacological approach that can be used to enhance the tolerogenic ability of immature DCs to prevent detrimental autoimmune responses.
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent9 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1124/jpet.106.103259
dc.identifier.eissn1521-0103
dc.identifier.issn0022-3565
dc.identifier.pubmedidMEDLINE:16597709
dc.identifier.urihttps://doi.org/10.1124/jpet.106.103259
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79457
dc.identifier.wosidWOS:000238437000008
dc.information.autorucCiencias Biológicas;Bronfman M;S/I;98819
dc.information.autorucCiencias Biológicas;Kalergis A;S/I;90610
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final67
dc.pagina.inicio59
dc.publisherAMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
dc.revistaJOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
dc.rightsacceso restringido
dc.subjectACTIVATED RECEPTOR-GAMMA
dc.subjectREGULATORY T-CELLS
dc.subjectIMMUNE-RESPONSES
dc.subjectPPAR-GAMMA
dc.subjectINFLAMMATION
dc.subjectSTIMULATION
dc.subjectGENERATION
dc.subjectEXPRESSION
dc.subjectMATURATION
dc.subjectCOMPLEX
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInhibition of nuclear factor-kappa B enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis
dc.typeartículo
dc.volumen318
sipa.codpersvinculados98819
sipa.codpersvinculados90610
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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