| First Author | Honke N | Year | 2013 |
| Journal | PLoS Pathog | Volume | 9 |
| Issue | 10 | Pages | e1003650 |
| PubMed ID | 24204252 | Mgi Jnum | J:247292 |
| Mgi Id | MGI:5918495 | Doi | 10.1371/journal.ppat.1003650 |
| Citation | Honke N, et al. (2013) Usp18 driven enforced viral replication in dendritic cells contributes to break of immunological tolerance in autoimmune diabetes. PLoS Pathog 9(10):e1003650 |
| abstractText | 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(+) T cells. Preventing enforced virus replication by depletion of CD11c(+) cells, genetically deleting Usp18, or pharmacologically inhibiting of viral replication blunted the expansion of autoreactive CD8(+) 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. |
