Skip to main content
eScholarship
Open Access Publications from the University of California

Usp18 driven enforced viral replication in dendritic cells contributes to break of immunological tolerance in autoimmune diabetes.

  • Author(s): Honke, Nadine
  • Shaabani, Namir
  • Zhang, Dong-Er
  • Iliakis, George
  • Xu, Haifeng C
  • Häussinger, Dieter
  • Recher, Mike
  • Löhning, Max
  • Lang, Philipp A
  • Lang, Karl S
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812017/
No data is associated with this publication.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item