Abstract 17775: Foxo3a Regulates Response to Coxsackievirus B3 Myocarditis via microRNA-155 Triggered NK-cell Activity

Background: FoxO3a is a transcription factor crucial in regulation of cell metabolism, stress resistance and immunity. Recently polymorphisms of FOXO3a have been associated with favorable outcome in inflammatory disease. However, mechanistic insight in FoxO3a effects is still limited. Here, we investigated the role of FoxO3a on NK-cell responses in viral myocarditis. Methods: A mouse model of Coxsackie Virus B3 (CVB3) myocarditis in wild-type and FoxO3a-/- mice was used to investigate the effects of FoxO3a on viral load and inflammation. Characterization of NK cells was performed by cytotoxic assay, surface marker- and interferon expression. Results: FoxO3a-/- mice showed significantly reduced myocardial inflammation, lower viral titers and attenuated expression of pro-inflammatory cytokines compared to wild-type mice 7 days post infection. Viral titers were significantly lower in FoxO3a-/- mice at day 3 while IFN γ and NKp46 expression were up-regulated within the heart suggesting early viral control by ...