Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation

J Exp Med. 2022 Jan 3;219(1):e20211083. doi: 10.1084/jem.20211083. Epub 2021 Nov 9.


The interaction between neutrophils and endothelial cells is critical for the pathogenesis of vascular inflammation. However, the regulation of neutrophil adhesive function remains not fully understood. Intravital microscopy demonstrates that neutrophil DREAM promotes neutrophil recruitment to sites of inflammation induced by TNF-α but not MIP-2 or fMLP. We observe that neutrophil DREAM represses expression of A20, a negative regulator of NF-κB activity, and enhances expression of pro-inflammatory molecules and phosphorylation of IκB kinase (IKK) after TNF-α stimulation. Studies using genetic and pharmacologic approaches reveal that DREAM deficiency and IKKβ inhibition significantly diminish the ligand-binding activity of β2 integrins in TNF-α-stimulated neutrophils or neutrophil-like HL-60 cells. Neutrophil DREAM promotes degranulation through IKKβ-mediated SNAP-23 phosphorylation. Using sickle cell disease mice lacking DREAM, we show that hematopoietic DREAM promotes vaso-occlusive events in microvessels following TNF-α challenge. Our study provides evidence that targeting DREAM might be a novel therapeutic strategy to reduce excessive neutrophil recruitment in inflammatory diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Gene Expression Regulation
  • HL-60 Cells
  • Humans
  • I-kappa B Kinase / metabolism
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Kv Channel-Interacting Proteins / genetics*
  • Kv Channel-Interacting Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microvessels / metabolism*
  • Microvessels / pathology
  • NF-kappa B / metabolism
  • Neutrophil Infiltration / drug effects
  • Neutrophil Infiltration / genetics*
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Phosphorylation / drug effects
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology


  • KCNIP3 protein, human
  • Kv Channel-Interacting Proteins
  • NF-kappa B
  • Repressor Proteins
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3