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- Title
<i>Usp18</i> Driven Enforced Viral Replication in Dendritic Cells Contributes to Break of Immunological Tolerance in Autoimmune Diabetes.
- Authors
Honke, Nadine; Shaabani, Namir; Zhang, Dong-Er; Iliakis, George; Xu, Haifeng C.; Häussinger, Dieter; Recher, Mike; Löhning, Max; Lang, Philipp A.; Lang, Karl S.
- 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+ 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.
- Subjects
VIRAL replication; DENDRITIC cells; DIABETES; AUTOIMMUNE diseases; CD8 antigen; CD11 antigen; AUTOIMMUNITY; IMMUNOLOGY
- Publication
PLoS Pathogens, 2013, Vol 9, Issue 10, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1003650