Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation.

Autor:	Li J; Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL., Kumari T; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Barazia A; Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL., Jha V; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Jeong SY; Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL., Olson A; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Kim M; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX., Lee BK; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX., Manickam V; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Song Z; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Clemens R; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Razani B; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.; Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; John Cochran VA Medical Center, St. Louis, MO., Kim J; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX., Dinauer MC; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Cho J; Department of Pharmacology, University of Illinois at Chicago College of Medicine, Chicago, IL.; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Jan 03; Vol. 219 (1). Date of Electronic Publication: 2021 Nov 09.
DOI:	10.1084/jem.20211083
Abstrakt:	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. Competing Interests: Disclosures: The authors declare no competing interests exist. (© 2021 Li et al.)
Databáze:	MEDLINE
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