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Interferon Regulatory Factor-9 (Irf-9) Mediates Short Term Host Protection, But Promotes Long Term Immune Injury in Evolution of Myocarditis Leading to Dilated Cardiomyopathy

Evolution of viral myocarditis to dilated cardiomyopathy (DCM)represents a delicate balance between host innate immunity and T-cell acquired immunity. IRF-9 is a key member of a transcription factor family that regulates type I interferon (IFN) production, critical for innate antiviral protection.
RESULTS: IRF9-/- mice showed dramatically increased mortality compared to the wildtype
littermates (0% WT vs 72% IRF-9-/- on day 14, P<0.0001). On day 42, there was
less cardiac hypertrophy and inflammation in IRF-9-/- mice compared to WT controls
(p<0.05). Onn day 42 there was a dramatic increase in the number of cytotoxic and
helper T-Cells in the wild-type mice that was not observed in the IRF-9-/- spleens
(p<0.05).
CONCLUSIONS: These data suggest a novel dual role of IRF-9 in not only regulating
interferon in acute stage of viral infection in myocarditis, but also late acquired immunity activation, including CD4/8 populations, contributing to the development of chronic cardiomyopathy.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30051
Date17 November 2011
CreatorsKonviser, Michael Joshua
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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