@article{0b9386f83e4b4a5dad9ac6e81c0d41df,
title = "NET formation is a default epigenetic program controlled by PAD4 in apoptotic neutrophils",
abstract = "Neutrophil extracellular traps (NETs) not only counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptor–mediated apoptosis promote gasdermin E (GSDME)–dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end of life for neutrophils.",
author = "Zhu, {Yanfang Peipei} and Mary Speir and Tan, {Zhe Hao} and Lee, {Jamie Casey} and Nowell, {Cameron J.} and Chen, {Alyce A.} and Hajera Amatullah and Salinger, {Ari J.} and Huang, {Carolyn J.} and Gio Wu and Weiqi Peng and Kasra Askari and Eric Griffis and Majid Ghassemian and Jennifer Santini and Motti Gerlic and Kiosses, {William B.} and Catz, {Sergio D.} and Hoffman, {Hal M.} and Greco, {Kimberly F.} and Edie Weller and Thompson, {Paul R.} and Wong, {Lai Ping} and Ruslan Sadreyev and Jeffrey, {Kate L.} and Croker, {Ben A.}",
note = "Funding Information: This work was supported by National Institutes of Health grant 5RO1HL124209 (B.A. C.), National Institutes of Health grant R01AI155869 (B.A.C. and H.M.H.), National Institutes of Health grant P01HL152958 (B.A.C., H.M.H., and S.D.C.), National Institutes of Health grant R35 GM118112 (P.R.T.), American Asthma Foundation (B.A.C.), Alpha-1 Foundation grant #615533 (M.Ge.), ISF grant #818/18 (M.Ge.), Israel Cancer Association Grant # 20220099 (M.Ge.), Varda and Boaz Dotan Research Center in Hemato-Oncology (M.Ge.), US-BSF grant #2017176 (B.A.C. and M.Ge.), National Institutes of Health grant 1U54HD0902565, Kenneth Rainin Foundation Innovator and Synergy Award (KLJ). National Institutes of Health grant R21AI144877 (KLJ). National Institutes of Health grant R01DK119996 (K.L.J.), National Institutes of Health grant UL 1TR002541, American Heart Association Career Development Award (Y.P.Z.), National Institutes of Health grant P30DK040561 (R.S.), National Institutes of Health grant NINDS P30 NS047101 (J. S.), National Cancer Institute Cancer Center Support grant 3P30CA006516-52 (C.J.H.), National Institutes of Health S10D021831, and UCSD-CMM-EM Core, RRID: SCR_022039, S10OD023527. Publisher Copyright: Copyright {\textcopyright} 2023 The Authors, some rights reserved.",
year = "2023",
month = dec,
day = "20",
doi = "10.1126/sciadv.adj1397",
language = "English",
volume = "9",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science (AAAS)",
number = "51",
}