Interferons promote autophagy via the STAT1/STAT5B-SOCS1 axis

Here, we show that IFN activates autophagy via STAT1/5B heterodimer-mediated upregulation of SOCS1 and contributes to virus-induced autophagy. Our data demonstrate that autophagic flux activation by type I and II IFNs peaks at 24 h post treatment, whereas type III IFNs induce autophagy with slower kinetics.

Mechanistically, IFN-mediated autophagy induction is dependent on JAK1-3 and both STAT1 as well as STAT5B. We show that STAT1 and STAT5B form heterodimers and co-localize following IFN treatment. Transcriptome analyses revealed that SOCS1 is induced in a STAT5B-dependent manner, and depletion of SOCS1 prevented IFN-induced autophagy.