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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

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.

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 YearPMID: 25564676


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

ATP-sensitive potassium channels mediate survival during infection in mammals and insects
The Kcnj8 potassium channel provides cardiovascular stability during inflammatory responses. Mutations in Kcnj8 are linked to Sudden Infant Death Syndrome (SIDS).

Croker et al., ATP-sensitive potassium channels mediate survival during infection in mammals and insects. Nature Genetics 2007, Dec 39: 1453-60. PMID: 18026101

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

  5. Ben 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. Ben 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. Ben 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. Ben 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 Immunology2010,185:2125-33. PMID:20644172

  16. Seth Masters, Lisa Mielke, Ann Cornish, Catherine Sutton, Joanne O’Donnell, Louise Cengia, Andrew Roberts, Ian Wicks, Kingston Mills, Ben 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. Ben 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. Ben Croker et al. Towards a four-dimensional view of neutrophils. Leucocytes: Methods and Protocols. Humana Press 2012, 844: 87-99. PMID:22262436

  20. Ben 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

  21. 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

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

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

  24. 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

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

  26. 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.

  27. 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

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

  29. 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

  30. Ben 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​

  31. Andrew J. Murphy et al., IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome. Cell Metab2016 Jan 12;23(1):155-64. PMID: 26603191

  32. 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

  33. 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

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

  35. 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.

  36. 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

  37. 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

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

  39. 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.

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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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: 31819256Comment in Science 2020, 367(6475): 261-262.