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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.

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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

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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. 

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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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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 
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Mini Lung Croker Leibel UCSD PNAS.png

  1. BA Croker et al. Rac2 deficient mice display perturbed T cell distribution and chemotaxis, but only minor abnormalities in TH1 responses. Immun Cell Biol 2002, 80, 231-40. PMID: 12067410

  2. BA Croker et al. The Rac2 GTPase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes. J Immunol 2002, 168, 3376-86. PMID:11907095

  3. BA Croker and Nicos Nicola. Cancer Drug Discovery and Development, Hematopoietic Growth Factors in Oncology: Basic Science and Clinical Therapeutics. The Jak-Stat Pathway of Cytokine Signaling. Humana Press.

  4. BA Croker et al. SOCS3 negatively regulates IL-6 signaling in vivo. Nature Immunology 2003, 4, 540-5. PMID: 12754505

  5. BA Croker et al. SOCS3 is a critical physiological negative regulator of G-CSF signaling and emergency granulopoiesis. Immunity 2004, 20, 153-165. PMID: 14975238

  6. Ben Emery et al. Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination. PNAS 2006, 103:7859-64. PMID:16682639

  7. Peter Wong et al. SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis. J Clin Invest 2006, 116: 1571-81. PMID:16710471

  8. Warren Alexander et al. Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene. PNAS 2006, 103:16442-7. PMID:17062753

  9. George Yeoh et al. Opposing roles of gp130 mediated STAT-3 and ERK-1/2 signalling in liver progenitor cell migration and proliferation. Hepatology 2007; 45:486-94. PMID:17256754

  10. Jo Eyles et al. A key role for G-CSF-induced neutrophil production and trafficking during inflammatory arthritis. Blood 2008, 112: 5193-5201. PMID:18824600

  11. BA Croker et al. Socs3 maintains the specificity of biological responses to cytokine signals during granulocyte and macrophage differentiation. Experimental Hematology 2008, 36, 786-798. PMID:18400361

  12. BA Croker et al. Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, Myd88, and a microbial trigger. PNAS 2008, 105:15028. PMID:18806225

  13. BA Croker et al. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 2008, 19:414-422. PMID:18708154

  14. Micha Berger et al. A Slfn2 mutation causes lymphoid and myeloid immunodeficiency due to loss of immune cell quiescence. Nature Immunology 2010, 11:335-43. PMID:20190759

  15. Yifan Zhan et al. Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways. J Immunology 2010,185:2125-33. PMID:20644172

  16. Seth Masters, Lisa Mielke, Ann Cornish, Catherine Sutton, Joanne O’Donnell, Louise Cengia, Andrew Roberts, Ian Wicks, Kingston Mills, BA Croker. Regulation of IL-1b by IFNg is species-specific, limited by SOCS1 and influences IL-17 production. EMBO reports 2010, 11:640-6. PMID:20596075

  17. BA Croker et al. Neutrophils require SHP1 to regulate IL-1β production and prevent inflammatory skin disease. J Immunology 2011 186:1131-9. PMID:21160041

  18. Michelle Tate et al. The role of neutrophils during mild and severe influenza virus infections of mice. PLOS One 2011, 6:e17618. PMID:21423798.

  19. BA Croker et al. Fas-mediated neutrophil apoptosis is accelerated by Bid, Bak and Bax and inhibited by Bcl-2 and Mcl-1. PNAS 2011, 108:13135-40. PMID:21768356

  20. Masters et al., NLRP1 activation induces pyroptosis of hematopoietic progenitor cells. Immunity 2012, 37: 1009. PMID: 23219391

  21. BA Croker et al. Towards a four-dimensional view of neutrophils. Leucocytes: Methods and Protocols. Humana Press 2012, 844: 87-99. PMID:22262436

  22. BA Croker et al. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3. Immunology and Cell Biology 2012, 90:124-9. PMID:21519345

  23. Lisa Lindqvist et al. Multiple mechanisms drive the induction of hematopoietic cell death by translation inhibitors: minor contribution of Mcl-1 reduction. Cell Death Diff 2012, 3:e409. PMID:23059828

  24. BA Croker et al. Pyroptotic death storms and cytopenia. Current Opinion in Immunology. 2013, 26: 128-137. PMID:24556409

  25. BA Croker. Neutrophil life in the death zone. Blood (Inside Blood) 2014 Jan 16;123(3):307-8. PMID:24434994

  26. X. Liu et al., Key role of suppressor of cytokine signaling 3 in regulating gp130 cytokine-induced signaling and limiting chondrocyte responses during murine inflammatory arthritis. Arthritis Rheumatol. 2014, 66:2391-402. PMID: 24839265

  27. Motti Gerlic et al. NLRP1a Expression in Srebp-1a-Deficient Mice. Cell Metab. 2014, 19(3):345-6. PMID: 24606891

  28. Joanne A O'Donnell et al. Fas regulates neutrophil lifespan during viral and bacterial infection. J Leukoc Biol 2015, 97 (2): 321-6. PMID:25473101.

  29. Man Lyang Kim et al. Aberrant actin depolymerization triggers the pyrin inflammasome and autoinflammatory disease that is dependent on IL-18, not IL-1β. J Exp Med 2015, 212: 927-38. PMID: 26008898

  30. KE Lawlor et al., RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nature Communications 2015, 18:6282. PMID: 25693118

  31. X. Liu et al., Distinctive pro-inflammatory gene signatures induced in articular chondrocytes by oncostatin M and IL-6 are regulated by Suppressor of Cytokine Signaling-3. Osteoarthritis Cartilage 2015, S1063-4584(15)01168-1. PMID: 26045176

  32. BA Croker et al., Fight or flight: regulation of emergency hematopoiesis by pyroptosis and necroptosis. Curr Opin Hematol. 2015 Jul;22(4):293-301.PMID: 26049749​

  33. Andrew J. Murphy et al., IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome. Cell Metab. 2016 Jan 12;23(1):155-64. PMID: 26603191

  34. M. Bliss-Moreau et al., A motive for killing: effector functions of regulated lytic cell death. Immunol Cell Biol. 2017 Feb;95(2):146-151. PMID: 27826146

  35. Melanie L. Hutton et al., A Helicobacter pylori Homolog of Eukaryotic Flotillin Is Involved in Cholesterol Accumulation, Epithelial Cell Responses and Host Colonization. Front Cell Infect Microbiol. 2017 Jun 6;7:219. PMID: 28634572

  36. S. Zargarian et al., Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. PLoS Biol. 2017 Jun 26;15(6):e2002711. PMID: 28650960

  37. Kate McArthur et al., Defining a therapeutic window for kinase inhibitors in leukemia to avoid neutropenia. Oncotarget 2017, Jul 28;8(35):57948-57963. PMID:28938529.

  38. JD Waight et al., Selective FcγR co-engagement on APCs modulates the activity of therapeutic antibodies targeting T cell antigens. Cancer Cell. 2018; 33, 1033. PMID: 29894690

  39. KW Chen et al., Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1β Secretion. J Immunology. 2018 May 15; 200 (10): 3341-3346. PMID: 29661823

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

  41. I Shlomovitz et al., Necroptosis directly induces the release of full-length biologically active IL-33 in vitro and in an inflammatory disease model. FEBS J. 2018 Dec 21. PMID: 30576068.

  42. BA Croker & M Kelliher. BID-ding on necroptosis in MDS. Blood 2019 Jan 10;133(2):103-104. PMID: 30630845. 

  43. X Liu, AA D'Cruz, J Hansen, BA Croker, KE Lawlor, NA Sims, IP Wicks. Deleting Suppressor of Cytokine Signaling-3 in chondrocytes reduces bone growth by disrupting mitogen-activated protein kinase signaling. Osteoarthritis Cartilage. 2019 Jun 5. pii: S1063-4584(19)31062-3. PMID: 31176017

  44. K Hanlon, A Thompson, L Pantano, JN Hutchinson, A Al-Obeidi, S Wang, M Bliss-Moreau, J Helble, G Alexe, K Stegmaier, DE Bauer, BA Croker.  Single-cell cloning of human T-cell lines reveals clonal variation in cell death responses to chemotherapeutics. Cancer Genetics 2019, 237:69-77. PMID: 31447068

  45. L Broderick, S Yost, D Li, M McGeough, L Boosherhi, M Guaderrama, S Brydges, K Kucharova, N Patel, M Harr, H Hakonarson, E Zackai, I Cowell, C Austin, B Hugle, C Gebauer, J Zhang, X Xu, J Wang, BA Croker, K Frazer, C Putnam, H Hoffman. Mutations in topoisomerase 2beta result in a B cell immunodeficiency. Nature Communications 2019, 10(1):3644. PMID: 31409799

  46. V Pazhakh*, F Ellett*, BA Croker*, Joanne A. O’Donnell, L Pase, KE Schulze, RS Greulich, A Gupta, CC Reyes-Aldasoro, A Andrianopoulos, GJ Lieschke. β-glucan dependent shuttling of conidia from neutrophils to macrophages occurs during fungal infection establishment.  PLoS Biol 17(9): e3000113. *contributed equally. PMID: 31483778

  47. M Speir, CJ Nowell, AA Chen, JA O’Donnell, IS Shamie, PR Lakin, AA D’Cruz, RO Braun, JJ Babon, RS Lewis, M Bliss-Moreau, I Shlomovitz, S Wang, LH Cengia, AI Stoica, R Hakem, MA Kelliher, LA O’Reilly, H Patsiouras, KE Lawlor, E Weller, NE Lewis, AW Roberts, M Gerlic, BA Croker. 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.

  48. C Donado et al., A Two-Cell Model for IL-1b release mediated by death receptor signaling. Cell Reports 2020, 31(1): 107466. PMID: 32268091

  49. S Wang et al., Cholesterol 25-Hydroxylase inhibits SARS-CoV-2 and coronaviruses by depleting membrane cholesterol. EMBO J 2020, Sep 18: e2020106057. PMID: 32944968

  50. Mor et al., Multi-clonal SARS-CoV-2 neutralization by antibodies isolated from severe COVID-19 convalescent donors. PLOS Pathogens 2021, 17(2):e1009165. PMID:33571304

  51. Sandoval et al., The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection. bioRxiv 2021. doi:https://doi.org/10.1101/2021.03.22.436522. 

  52. Park et al., Interactions of SARS-CoV-2 envelope protein with amilorides correlate with antiviral activity. PLOS Pathogens 2021. 17(5): e1009519. PMID:34003853

  53. Freund et al., Walking down the memory lane with SARS-CoV-2 B cells. Immunology & Cell Biology 2021. http://doi.org/10.1111/imcb.12494 

  54. Wang et al., Inflammasome activation in children with Kawasaki Disease and Multisystem Inflammatory Syndrome. Arterioscler Thromb Vasc Biol. 2021, 15:ATVBAHA121316210. PMID: 34261329

  55. Z Inde*, BA Croker* et al. Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 disease severity. Science Advances 2021,7(34):eabf8609. *contributed equally. PMID:34407940

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

  57. Li et al., Conformational flexibility in neutralization of SARS-CoV-2 by naturally-elicited anti-SARS-CoV-2 antibodies. Communications Biology 2022, 5(1):789. PMID:35931732

  58. Kaufmann et al., NLRP3 activation in neutrophils induces lethal autoinflammation, liver inflammation, and fibrosis. EMBO Reports 2022. 23(11):e54446. PMID:36194627

  59. Zhu et al., NET formation is the default epigenetic program controlled by PAD4 in apoptotic neutrophils. Science Advances 2023. 9(51): eadj1397. PMID:38117877

  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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