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Usp18 Driven Enforced Viral Replication in Dendritic Cells Contributes to Break of Immunological Tolerance in Autoimmune Diabetes
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نویسنده
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honke n. ,shaabani n. ,zhang d.-e. ,iliakis g. ,xu h.c. ,häussinger d. ,recher m. ,löhning m. ,lang p.a. ,lang k.s.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 10
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چکیده
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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. © 2013 honke et al.
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آدرس
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institute of immunology,university of duisburg-essen,essen,germany,department of gastroenterology,hepatology and infectious diseases,heinrich-heine-university düsseldorf,düsseldorf, Germany, institute of immunology,university of duisburg-essen,essen,germany,department of gastroenterology,hepatology and infectious diseases,heinrich-heine-university düsseldorf,düsseldorf, Germany, department of pathology,division of biological sciences and moores ucsd cancer center,university of california,san diego,la jolla,ca, United States, institute of medical radiation biology,university of duisburg-essen,essen, Germany, institute of immunology,university of duisburg-essen,essen,germany,department of gastroenterology,hepatology and infectious diseases,heinrich-heine-university düsseldorf,düsseldorf, Germany, department of gastroenterology,hepatology and infectious diseases,heinrich-heine-university düsseldorf,düsseldorf, Germany, clinic for primary immunodeficiencies,medical outpatient unit,and immunobiology,department of biomedicine,university hospital basel,basel, Switzerland, department of rheumatology and clinical immunology,charité - university medicine berlin and german rheumatism research center (drfz),berlin, Germany, department of gastroenterology,hepatology and infectious diseases,heinrich-heine-university düsseldorf,düsseldorf, Germany, institute of immunology,university of duisburg-essen,essen,germany,department of gastroenterology,hepatology and infectious diseases,heinrich-heine-university düsseldorf,düsseldorf, Germany
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Authors
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