miR-155 Upregulation in Dendritic Cells Is Sufficient To Break Tolerance In Vivo by Negatively Regulating SHIP1.
J Immunol
; 195(10): 4632-40, 2015 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-26447227
TLR-induced maturation of dendritic cells (DCs) leads to the production of proinflammatory cytokines as well as the upregulation of various molecules involved in T cell activation. These are believed to be the critical events that account for the induction of the adaptive immune response. In this study, we have examined the role of miR-155 in DC function and the induction of immunity. Using a model in which the transfer of self-Ag-pulsed, TLR-matured DCs can induce a functional CD8 T cell response and autoimmunity, we find that DCs lacking miR-155 have an impaired ability to break immune tolerance. Importantly, transfer of self- Ag-pulsed DCs overexpressing miR-155 was sufficient to break tolerance in the absence of TLR stimuli. Although these unstimulated DCs induced T cell function in vivo, there was no evidence for the upregulation of costimulatory ligands or cytokine secretion. Further analysis showed that miR-155 influenced the level of the phosphatase SHIP1 in DCs and that the lack of SHIP1 in DCs was sufficient to break T cell tolerance in vivo, again in the absence of TLR-induced DC maturation. Our study demonstrates that the overexpression of miR-155 in DCs is a critical event that is alone sufficient to break self-tolerance and promote a CD8-mediated autoimmune response in vivo. This process is independent of the induction of conventional DC maturation markers, indicating that miR-155 regulation of SHIP represents a unique axis that regulates DC function in vivo.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Monoéster Fosfórico Hidrolasas
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MicroARNs
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Tolerancia Inmunológica
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2015
Tipo del documento:
Article