Usp18 Driven Enforced Viral Replication in Dendritic Cells Contributes to Break of Immunological Tolerance in Autoimmune Diabetes

作者：Honke Nadine^*; Shaabani Namir; Zhang Dong Er; Iliakis George; Xu Haifeng C; Haeussinger Dieter; Recher Mike; Loehning Max; Lang Philipp A; Lang Karl S

来源：PLoS Pathogens, 2013, 9(10): e1003650.

DOI：10.1371/journal.ppat.1003650

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.

• 出版日期2013-10
• 单位河北医科大学