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. 2017 Nov 20;43(4):449-462.e5.
doi: 10.1016/j.devcel.2017.10.013. Epub 2017 Nov 2.

Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps

Borko Amulic  1 , Sebastian Lorenz Knackstedt  1 , Ulrike Abu Abed  2 , Nikolaus Deigendesch  3 , Christopher J Harbort  1 , Brian E Caffrey  4 , Volker Brinkmann  5 , Frank L Heppner  6 , Philip W Hinds  7 , Arturo Zychlinsky  8
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Free article

Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps

Borko Amulic et al. Dev Cell. .
Free article

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.

Keywords: Candida albicans; Cdk6; NETs; innate immunity; neutrophil.

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