Usp18 driven enforced viral replication in dendritic cells contributes to break of immunological tolerance in autoimmune diabetes.
PLoS Pathog
; 9(10): e1003650, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-24204252
ABSTRACT
Infection with viruses carrying cross-reactive antigens is associated with break of immunological tolerance and induction of autoimmune disease. Dendritic cells play an important role in this process. However, it remains unclear why autoimmune-tolerance is broken during virus infection, but usually not during exposure to non-replicating cross-reactive antigens. Here we show that antigen derived from replicating virus but not from non-replicating sources undergoes a multiplication process in dendritic cells in spleen and lymph nodes. This enforced viral replication was dependent on Usp18 and was essential for expansion of autoreactive CD8⺠T cells. Preventing enforced virus replication by depletion of CD11c⺠cells, genetically deleting Usp18, or pharmacologically inhibiting of viral replication blunted the expansion of autoreactive CD8⺠T cells and prevented autoimmune diabetes. In conclusion, Usp18-driven enforced viral replication in dendritic cells can break immunological tolerance and critically influences induction of autoimmunity.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
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Células Dendríticas
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Ubiquitina Tiolesterasa
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Diabetes Mellitus Tipo 1
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Tolerancia Inmunológica
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Coriomeningitis Linfocítica
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Virus de la Coriomeningitis Linfocítica
Límite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Pathog
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania