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

doi:10.1016/j.devcel.2017.10.013

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

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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 language	English
Pages (from-to)	449-462.e5
Number of pages	19
Journal	Developmental Cell
Volume	43
Issue number	4
Early online date	2 Nov 2017
DOIs	https://doi.org/10.1016/j.devcel.2017.10.013
Publication status	Published - 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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10.1016/j.devcel.2017.10.013

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Dr Borko Amulic
- borko.amulicbristol.acuk
- School of Cellular and Molecular Medicine - Associate Professor in Immunology
- Infection and Immunity
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@article{59f488c27c2248fe9470dd5018483d9d,

title = "Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps",

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

author = "Borko Amulic and Knackstedt, \{Sebastian Lorenz\} and \{Abu Abed\}, Ulrike and Nikolaus Deigendesch and Harbort, \{Christopher J\} and Caffrey, \{Brian E\} and Volker Brinkmann and Heppner, \{Frank L\} and Hinds, \{Philip W\} and Arturo Zychlinsky",

year = "2017",

month = nov,

day = "20",

doi = "10.1016/j.devcel.2017.10.013",

language = "English",

volume = "43",

pages = "449--462.e5",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps

AU - Amulic, Borko

AU - Knackstedt, Sebastian Lorenz

AU - Abu Abed, Ulrike

AU - Deigendesch, Nikolaus

AU - Harbort, Christopher J

AU - Caffrey, Brian E

AU - Brinkmann, Volker

AU - Heppner, Frank L

AU - Hinds, Philip W

AU - Zychlinsky, Arturo

PY - 2017/11/20

Y1 - 2017/11/20

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Cycle

KW - Cyclin-Dependent Kinase 4

KW - Cyclin-Dependent Kinase 6

KW - Extracellular Traps

KW - Mice, Transgenic

KW - Neutrophil Activation

KW - Neutrophils

KW - Phosphorylation

KW - Retinoblastoma Protein

KW - Journal Article

U2 - 10.1016/j.devcel.2017.10.013

DO - 10.1016/j.devcel.2017.10.013

M3 - Article (Academic Journal)

C2 - 29103955

SN - 1534-5807

VL - 43

SP - 449-462.e5

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -

Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps

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