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IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features.
Gabriele, L; Fragale, A; Borghi, P; Sestili, P; Stellacci, E; Venditti, M; Schiavoni, G; Sanchez, M; Belardelli, F; Battistini, A.
Afiliación
  • Gabriele L; Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy.
J Leukoc Biol ; 80(6): 1500-11, 2006 Dec.
Article en En | MEDLINE | ID: mdl-16966383
Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Plasmáticas / Células Dendríticas / Diferenciación Celular / Factor 1 Regulador del Interferón / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Leukoc Biol Año: 2006 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Plasmáticas / Células Dendríticas / Diferenciación Celular / Factor 1 Regulador del Interferón / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Leukoc Biol Año: 2006 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido