Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps

Borko Amulic, Sebastian Lorenz Knackstedt, Ulrike Abu Abed, Nikolaus Deigendesch, Christopher J Harbort, Brian E Caffrey, Volker Brinkmann, Frank L Heppner, Philip W Hinds, Arturo Zychlinsky

Research output: Contribution to journalArticle (Academic Journal)peer-review

48 Citations (Scopus)
373 Downloads (Pure)

Abstract

Neutrophils are essential for immune defense and can respond to infection by releasing chromatin in the form of neutrophil extracellular traps (NETs). Here we show that NETs are induced by mitogens and accompanied by induction of cell-cycle markers, including phosphorylation of the retinoblastoma protein and lamins, nuclear envelope breakdown, and duplication of centrosomes. We identify cyclin-dependent kinases 4 and 6 (CDK4/6) as essential regulators of NETs and show that the response is inhibited by the cell-cycle inhibitor p21Cip. CDK6, in neutrophils, is required for clearance of the fungal pathogen Candida albicans. Our data describe a function for CDK4/6 in immunity.

Original languageEnglish
Pages (from-to)449-462.e5
Number of pages19
JournalDevelopmental Cell
Volume43
Issue number4
Early online date2 Nov 2017
DOIs
Publication statusPublished - 20 Nov 2017

Keywords

  • Animals
  • Cell Cycle
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Extracellular Traps
  • Mice, Transgenic
  • Neutrophil Activation
  • Neutrophils
  • Phosphorylation
  • Retinoblastoma Protein
  • Journal Article

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