CROKER LAB
Department of Pediatrics, UC San Diego
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.
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
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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
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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
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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.
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BA Croker et al. SOCS3 negatively regulates IL-6 signaling in vivo. Nature Immunology 2003, 4, 540-5. PMID: 12754505
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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
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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
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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
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Warren Alexander et al. Thrombocytopenia and kidney disease in mice with a mutation in the C1galt1 gene. PNAS 2006, 103:16442-7. PMID:17062753
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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
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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
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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
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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
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BA Croker et al. SOCS regulation of the JAK/STAT signalling pathway. Semin Cell Dev Biol 2008, 19:414-422. PMID:18708154
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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
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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
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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
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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
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Michelle Tate et al. The role of neutrophils during mild and severe influenza virus infections of mice. PLOS One 2011, 6:e17618. PMID:21423798.
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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
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Masters et al., NLRP1 activation induces pyroptosis of hematopoietic progenitor cells. Immunity 2012, 37: 1009. PMID: 23219391
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BA Croker et al. Towards a four-dimensional view of neutrophils. Leucocytes: Methods and Protocols. Humana Press 2012, 844: 87-99. PMID:22262436
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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
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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
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BA Croker et al. Pyroptotic death storms and cytopenia. Current Opinion in Immunology. 2013, 26: 128-137. PMID:24556409
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BA Croker. Neutrophil life in the death zone. Blood (Inside Blood) 2014 Jan 16;123(3):307-8. PMID:24434994
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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
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Motti Gerlic et al. NLRP1a Expression in Srebp-1a-Deficient Mice. Cell Metab. 2014, 19(3):345-6. PMID: 24606891
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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.
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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
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KE Lawlor et al., RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nature Communications 2015, 18:6282. PMID: 25693118
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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
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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
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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
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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
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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
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S. Zargarian et al., Phosphatidylserine externalization, "necroptotic bodies" release, and phagocytosis during necroptosis. PLoS Biol. 2017 Jun 26;15(6):e2002711. PMID: 28650960
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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.
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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
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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
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AA D’Cruz et al., The pseudokinase MLKL activates PAD4-dependent NET formation in necroptotic neutrophils. Science Signaling 2018, 11, eaao1716. PMID: 30181240.
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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.
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BA Croker & M Kelliher. BID-ding on necroptosis in MDS. Blood 2019 Jan 10;133(2):103-104. PMID: 30630845.
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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
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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
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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
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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
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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.
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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
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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
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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
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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.
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Park et al., Interactions of SARS-CoV-2 envelope protein with amilorides correlate with antiviral activity. PLOS Pathogens 2021. 17(5): e1009519. PMID:34003853
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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
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Wang et al., Inflammasome activation in children with Kawasaki Disease and Multisystem Inflammatory Syndrome. Arterioscler Thromb Vasc Biol. 2021, 15:ATVBAHA121316210. PMID: 34261329
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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
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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
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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
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Kaufmann et al., NLRP3 activation in neutrophils induces lethal autoinflammation, liver inflammation, and fibrosis. EMBO Reports 2022. 23(11):e54446. PMID:36194627
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Zhu et al., NET formation is the default epigenetic program controlled by PAD4 in apoptotic neutrophils. Science Advances 2023. 9(51): eadj1397. PMID:38117877
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Leibel et al., The lung employs an intrinsic surfactant-mediated inflammatory response for viral defense. PNAS 2024. 121 (30) e2408109121