Long non-coding RNA AK085865 ablation confers susceptibility to viral myocarditis by regulating macrophage polarization.

Accumulating evidence indicates that regulators of macrophage polarization may exert pivotal functions in the development of coxsackievirus B3 (CVB3)-induced viral myocarditis (VM). However, the mechanisms underlying macrophage polarization remain to be explored. Here, we sought to identify novel and functionally important long non-coding RNAs (lncRNAs) during macrophage polarization and to investigate their function and contribution to VM. In this study, we identified the lncRNA AK085865 as an important regulator of macrophage polarization. Knock-down of AK085865 diminished phenotypical expression of M2 macrophages while promoting polarization to the M1 phenotype. Moreover, AK085865-/- mice had increased susceptibility to CVB3-induced VM. We observed striking bias towards M1 macrophages, whereas the M2 population was decreased in AK085865-/- VM mice. Collectively, our findings uncover a critical role of AK085865 in the regulation of macrophage polarization in vitro and in vivo, identifying a new player in the development of VM and providing a potential clinically significant therapeutic target.