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Immunity ; 45(2): 305-18, 2016 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-27533013

RESUMEN

Dendritic cells (DCs) are instrumental in the initiation of T cell responses, but how thymic and peripheral tolerogenic DCs differ globally from Toll-like receptor (TLR)-induced immunogenic DCs remains unclear. Here, we show that thymic XCR1(+) DCs undergo a high rate of maturation, accompanied by profound gene-expression changes that are essential for central tolerance and also happen in germ-free mice. Those changes largely overlap those occurring during tolerogenic and, more unexpectedly, TLR-induced maturation of peripheral XCR1(+) DCs, arguing against the commonly held view that tolerogenic DCs undergo incomplete maturation. Interferon-stimulated gene (ISG) expression was among the few discriminators of immunogenic and tolerogenic XCR1(+) DCs. Tolerogenic XCR1(+) thymic DCs were, however, unique in expressing ISGs known to restrain virus replication. Therefore, a broad functional convergence characterizes tolerogenic and immunogenic XCR1(+) DC maturation in the thymus and periphery, maximizing antigen presentation and signal delivery to developing and to conventional and regulatory mature T cells.


Asunto(s)
Tolerancia Central , Células Dendríticas/inmunología , Tolerancia Periférica , Linfocitos T Reguladores/inmunología , Timo/inmunología , Animales , Presentación de Antígeno , Diferenciación Celular , Células Cultivadas , Factores Reguladores del Interferón/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Quimiocina/metabolismo , Receptores Toll-Like/inmunología , Transcriptoma , Replicación Viral
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