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NET formation is the default epigenetic program controlled by PAD4 in apoptotic neutrophils.
GSDME promotes PAD4 activation and DNA externalization from apoptotic neutrophils
Zhu et al., Science Advances 2023. 9(51): eadj1397. PMID:38117877
Comment in Science Advances 2023. 9(51): DOI: 10.1126/sciadv.adm8715
Neutrophils only die twice
Souza FW & Miao EA

Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation
Ptpn6 negatively regulates p38 MAPK activation to control TNF and IL-1α/β expression, and maintains Ripk1 function to prevent caspase-8- and Ripk3–Mlkl-dependent cell death and concomitant IL-1α/β release.


Speir et al. Ptpn6 inhibits caspase-8- and Ripk3/Mlkl-dependent inflammation. Nature Immunology 2020, 21, 54-64. PMID: 31819256

Comment in Science 2020, 367(6475): 261-262. 

Croker SHP1 Live Cell PTPN6 UCSD.png
Necroptotic NETS Croker2018 color.jpg
The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils
Neutrophil necroptosis generates a specialized form of neutrophil extracellular trap (NET)


A D’Cruz et al., The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils. Science Signaling, 11, eaao1716 (2018). PMID: 30181240

Immune response to IVIG in patients with Kawasaki disease & MIS-C
IVIG targets IL-1b+ neutrophils via non-apoptotic cell death


Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C. The Journal of Clinical Investigation 2021; 131(20):e147076. PMID: 34464357.

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