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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): Neutrophils only die twice, Souza FW & Miao EA
Commentary on cell death, Knowable Magazine, Amber Dance, Your cells are dying. All the time.

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.

SARS-CoV-2 infects diverse human lung cell types triggering production of interferon and chemokines, apoptotic cell death, and is neutralized by surfactant protein B.
SARS-CoV-2 strong cytopathic effect on human lung cells is a result of apoptosis
A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response. PNAS 2024, 121(30) e2408109121. PMID: 39028694 
Mini Lung Croker Leibel UCSD PNAS.png
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  60. Leibel et al., The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense. PNAS 2024. 121 (30) e2408109121

 

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