PAPERS

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. 

RIPK1 regulates RIPK3-MLKL driven systemic inflammation and emergency hematopoiesis
RIPK1 deficiency induces RIPK3- and Caspase-8-dependent deletion of hematopoietic stem cells and hematopoietic progenitor cells following transplantation

 

Rickard et al., RIPK1 regulates RIPK3-MLKL driven systemic inflammation and emergency hematopoiesis. Cell 2014, 157(5): 1175-88. PMID:24813849

 

Reviewed in Berndt et al., Science Signaling 2015, 8(358):1. 2014: Signaling Breakthroughs of the Year. PMID: 25564676

 

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

NLRP1 activation induces pyroptosis of hematopoietic progenitor cells
Systemic activation of NLRP1 induces multi-organ inflammation, cytopenia and immunosuppression

 

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

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

  21. 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

  22. 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

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

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

  25. 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

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

  27. 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.

  28. 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

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

  30. 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

  31. 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​

  32. 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

  33. 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

  34. 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

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

  36. 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.

  37. 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

  38. 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

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

  40. 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.

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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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.

 

Division of Rheumatology, Allergy & Immunology, Department of Pediatrics, School of Medicine, UC San Diego, 9500 Gilman Drive, La Jolla, California, United States

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