Histone deacetylase 3 contributes to the antiviral innate immunity of macrophages by interacting with FOXK1 to regulate STAT1/2 transcription

Cell Rep. 2022 Jan 25;38(4):110302. doi: 10.1016/j.celrep.2022.110302.


It is well known that interferon (IFN)-α/-β activates the JAK/STAT signaling pathway and suppresses viral replication through the induction of IFN stimulated genes (ISGs). Here, we report that knockout of HDAC3 from macrophages results in the decreased expression of STAT1 and STAT2, leading to defective antiviral immunity in cells and mice. Further studies show that HDAC3 interacts with a conserved transcription factor Forkhead Box K1 (FOXK1), co-localizes with FOXK1 at the promoter of STAT1 and STAT2, and is required for protecting FOXK1 from lysosomal system-mediated degradation. FOXK1-deficient macrophages also show low STAT1 and STAT2 expression with defective responses to viruses. Thus, our studies uncover the biological importance of HDAC3 in regulating the antiviral immunity of macrophages through interacting with FOXK1 to regulate the expression of STAT1 and STAT2.

Keywords: FOXK1; HDAC3; STAT1; STAT2; transcription regulation; type I interferon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Forkhead Transcription Factors / immunology
  • Gene Expression Regulation / immunology*
  • Histone Deacetylases / immunology*
  • Immunity, Innate / immunology*
  • Macrophages / immunology*
  • Mice
  • STAT1 Transcription Factor / biosynthesis
  • STAT1 Transcription Factor / immunology
  • STAT2 Transcription Factor / biosynthesis
  • STAT2 Transcription Factor / immunology
  • Transcription, Genetic
  • Virus Diseases / immunology*


  • Forkhead Transcription Factors
  • Foxk1 protein, mouse
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Histone Deacetylases
  • histone deacetylase 3