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The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation

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Abstract

ARTS (Sept4_i2) is a pro-apoptotic protein and a product of the Sept4 gene. ARTS acts upstream of mitochondria to initiate caspase activation. ARTS induces apoptosis by specifically binding XIAP and allowing de-repression of active caspases required for Mitochondrial Outer Membrane Permeabilzation (MOMP). Moreover, ARTS promotes apoptosis by inducing ubiquitin-mediated degradation of both major anti-apoptotic proteins XIAP and Bcl-2. In the resolution phase of inflammation, the infiltrating leukocytes, which execute the acute innate response, undergo apoptosis and are subsequently cleared by phagocytic macrophages (i.e. efferocytosis). In this course, macrophages undergo reprogramming from inflammatory, to anti-inflammatory, and eventually to resolving macrophages that leave the injury sites. Since engulfment of apoptotic leukocytes is a key signaling step in macrophage reprogramming and resolution of inflammation, we hypothesized that a failed apoptosis in leukocytes in vivo would result in an impaired resolution process. To test this hypothesis, we utilized the Sept4/ARTS−/− mice, which exhibit resistance to apoptosis in many cell types. During zymosan A-induced peritonitis, Sept4/ARTS−/− mice exhibited impaired resolution of inflammation, characterized by reduced neutrophil apoptosis, macrophage efferocytosis and expression of pro-resolving mediators. This was associated with increased pro-inflammatory cytokines and reduced anti-inflammatory cytokines, secreted by resolution-phase macrophages. Moreover, ARTS overexpression in leukocytes in vitro promoted an anti-inflammatory behavior. Overall, our results suggest that ARTS is a key master-regulator necessary for neutrophil apoptosis, macrophage efferocytosis and reprogramming to the pro-resolving phenotype during the resolution of inflammation.

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References

  1. Fuchs Y, Steller H (2011) Programmed cell death in animal development and disease. Cell 147:742–758

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Meier P, Finch A, Evan G (2000) Apoptosis in development. Nature 407:796–801

    CAS  PubMed  Google Scholar 

  3. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    CAS  PubMed  Google Scholar 

  4. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

    CAS  PubMed  Google Scholar 

  6. Donepudi M, Grutter MG (2002) Structure and zymogen activation of caspases. Biophys Chem 101–102:145–153

    PubMed  Google Scholar 

  7. Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281:1312–1316

    CAS  PubMed  Google Scholar 

  8. McComb S, Chan PK, Guinot A et al (2019) Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7. Sci Adv 5:eaau9433

    PubMed  PubMed Central  Google Scholar 

  9. Ramirez MLG, Salvesen GS (2018) A primer on caspase mechanisms. Semin Cell Dev Biol 82:79–85

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    CAS  PubMed  Google Scholar 

  11. Eckelman BP, Salvesen GS (2006) The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 281:3254–3260

    CAS  PubMed  Google Scholar 

  12. Salvesen GS, Duckett CS (2002) IAP proteins: blocking the road to death's door. Nat Rev Mol Cell Biol 3:401–410

    CAS  PubMed  Google Scholar 

  13. Deveraux QL, Reed JC (1999) IAP family proteins-suppressors of apoptosis. Genes Dev 13:239–252

    CAS  PubMed  Google Scholar 

  14. Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, Reed JC (1999) Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 18:5242–5251

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R (2001) X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. J Biol Chem 276:27058–27063

    CAS  PubMed  Google Scholar 

  16. Gyrd-Hansen M, Darding M, Miasari M et al (2008) IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis. Nat Cell Biol 10:1309–1317

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Schile AJ, Garcia-Fernandez M, Steller H (2008) Regulation of apoptosis by XIAP ubiquitin-ligase activity. Genes Dev 22:2256–2266

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Rajalingam K, Dikic I (2009) Inhibitors of apoptosis catch ubiquitin. Biochem J 417:e1–3

    CAS  PubMed  Google Scholar 

  19. Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM (2000) ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol 10:1359–1366

    CAS  PubMed  Google Scholar 

  20. Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    CAS  PubMed  Google Scholar 

  21. Verhagen AM, Ekert PG, Pakusch M et al (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43–53

    CAS  PubMed  Google Scholar 

  22. Hegde R, Srinivasula SM, Zhang Z et al (2002) Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J Biol Chem 277:432–438

    CAS  PubMed  Google Scholar 

  23. Yin W, Cheepala S, Clifford JL (2006) Identification of a novel splice variant of X-linked inhibitor of apoptosis-associated factor 1. Biochem Biophys Res Commun 339:1148–1154

    CAS  PubMed  Google Scholar 

  24. Larisch S, Yi Y, Lotan R et al (2000) A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol 2:915–921

    CAS  PubMed  Google Scholar 

  25. van Loo G, van Gurp M, Depuydt B et al (2002) The serine protease Omi/HtrA2 is released from mitochondria during apoptosis. Omi interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 9:20–26

    PubMed  Google Scholar 

  26. Leaman DW, Chawla-Sarkar M, Vyas K et al (2002) Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis. J Biol Chem 277:28504–28511

    CAS  PubMed  Google Scholar 

  27. Gottfried Y, Rotem A, Lotan R, Steller H, Larisch S (2004) The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. EMBO J 23:1627–1635

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Mandel-Gutfreund Y, Kosti I, Larisch S (2011) ARTS, the unusual septin: structural and functional aspects. Biol Chem 392:783–790

    CAS  PubMed  Google Scholar 

  29. Edison N, Zuri D, Maniv I et al (2012) The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo. Cell Death Differ 19:356–368

    CAS  PubMed  Google Scholar 

  30. Lotan R, Rotem A, Gonen H et al (2005) Regulation of the proapoptotic ARTS protein by ubiquitin-mediated degradation. J Biol Chem 280:25802–25810

    CAS  PubMed  Google Scholar 

  31. Elhasid R, Sahar D, Merling A et al (2004) Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients. Oncogene 23:5468–5475

    CAS  PubMed  Google Scholar 

  32. Edison N, Curtz Y, Paland N et al (2017) Degradation of Bcl-2 by XIAP and ARTS promotes apoptosis. Cell Rep 21:442–454

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Abbas R, Larisch S (2020) Targeting XIAP for Promoting Cancer Cell Death-The Story of ARTS and SMAC. Cells 9(3):663

    PubMed Central  Google Scholar 

  34. Garrison JB, Correa RG, Gerlic M et al (2011) ARTS and Siah collaborate in a pathway for XIAP degradation. Mol Cell 41:107–116

    CAS  PubMed  Google Scholar 

  35. Edison N, Curtz Y, Paland N et al (2017) Degradation of Bcl-2 by XIAP and ARTS Promotes Apoptosis. Cell Reports 21:442–454

    CAS  PubMed  Google Scholar 

  36. Garcia-Fernandez M, Kissel H, Brown S et al (2010) Sept4/ARTS is required for stem cell apoptosis and tumor suppression. Genes Dev 24:2282–2293

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Koren E, Yosefzon Y, Ankawa R et al (2018) ARTS mediates apoptosis and regeneration of the intestinal stem cell niche. Nat Commun 9:4582

    PubMed  PubMed Central  Google Scholar 

  38. Fuchs Y, Brown S, Gorenc T, Rodriguez J, Fuchs E, Steller H (2013) Sept4/ARTS regulates stem cell apoptosis and skin regeneration. Science 341:286–289

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Koren E, Fuchs Y (2019) The ARTS of Cell Death. J Cell Death 12:1179066019836967

    PubMed  PubMed Central  Google Scholar 

  40. Ariel A, Timor O (2013) Hanging in the balance: endogenous anti-inflammatory mechanisms in tissue repair and fibrosis. J Pathol 229:250–263

    CAS  PubMed  Google Scholar 

  41. Headland SE, Norling LV (2015) The resolution of inflammation: Principles and challenges. Semin Immunol 27:149–160

    CAS  PubMed  Google Scholar 

  42. Greenlee-Wacker MC (2016) Clearance of apoptotic neutrophils and resolution of inflammation. Immunol Rev 273:357–370

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Ariel A, Serhan CN (2012) New Lives Given by Cell Death: Macrophage Differentiation Following Their Encounter with Apoptotic Leukocytes during the Resolution of Inflammation. Front Immunol 3:4

    PubMed  PubMed Central  Google Scholar 

  44. Elliott MR, Koster KM, Murphy PS (2017) Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses. J Immunol 198:1387–1394

    CAS  PubMed  Google Scholar 

  45. Campbell L, Saville CR, Murray PJ, Cruickshank SM, Hardman MJ (2013) Local arginase 1 activity is required for cutaneous wound healing. J Invest Dermatol 133:2461–2470

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Freire-de-Lima CG, Xiao YQ, Gardai SJ, Bratton DL, Schiemann WP, Henson PM (2006) Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J Biol Chem 281:38376–38384

    CAS  PubMed  Google Scholar 

  47. Dalli J, Serhan CN (2017) Pro-resolving mediators in regulating and conferring macrophage function. Front Immunol 8:1400

    PubMed  PubMed Central  Google Scholar 

  48. Schif-Zuck S, Gross N, Assi S, Rostoker R, Serhan CN, Ariel A (2011) Saturated-efferocytosis generates pro-resolving CD11b low macrophages: modulation by resolvins and glucocorticoids. Eur J Immunol 41:366–379

    CAS  PubMed  Google Scholar 

  49. Lin N, Shay JES, Xie H et al (2018) Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis. Front Immunol 9:2565

    PubMed  PubMed Central  Google Scholar 

  50. Yamada T, Tani Y, Nakanishi H, Taguchi R, Arita M, Arai H (2011) Eosinophils promote resolution of acute peritonitis by producing proresolving mediators in mice. FASEB J 25:561–568

    CAS  PubMed  Google Scholar 

  51. Isobe Y, Kato T, Arita M (2012) Emerging roles of eosinophils and eosinophil-derived lipid mediators in the resolution of inflammation. Front Immunol 3:270

    PubMed  PubMed Central  Google Scholar 

  52. Ueha S, Shand FH, Matsushima K (2012) Cellular and molecular mechanisms of chronic inflammation-associated organ fibrosis. Front Immunol 3:71

    PubMed  PubMed Central  Google Scholar 

  53. Gieseck RL 3rd, Wilson MS, Wynn TA (2018) Type 2 immunity in tissue repair and fibrosis. Nat Rev Immunol 18:62–76

    CAS  PubMed  Google Scholar 

  54. Krzyszczyk P, Schloss R, Palmer A, Berthiaume F (2018) The role of macrophages in acute and chronic wound healing and interventions to promote pro-wound healing phenotypes. Front Physiol 9:419

    PubMed  PubMed Central  Google Scholar 

  55. Bratton DL, Henson PM (2011) Neutrophil clearance: when the party is over, clean-up begins. Trends Immunol 32:350–357

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hughes JE, Srinivasan S, Lynch KR, Proia RL, Ferdek P, Hedrick CC (2008) Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circ Res 102:950–958

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Weigert A, Johann AM, von Knethen A, Schmidt H, Geisslinger G, Brune B (2006) Apoptotic cells promote macrophage survival by releasing the antiapoptotic mediator sphingosine-1-phosphate. Blood 108:1635–1642

    CAS  PubMed  Google Scholar 

  58. Pashover-Schallinger E, Aswad M, Schif-Zuck S, Shapiro H, Singer P, Ariel A (2012) The atypical chemokine receptor D6 controls macrophage efferocytosis and cytokine secretion during the resolution of inflammation. FASEB J 26:3891–3900

    CAS  PubMed  Google Scholar 

  59. Ariel A, Fredman G, Sun YP et al (2006) Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol 7:1209–1216

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Graham GJ, McKimmie CS (2006) Chemokine scavenging by D6: a movable feast? Trends Immunol 27:381–386

    CAS  PubMed  Google Scholar 

  61. Martinez de la Torre Y, Locati M, Buracchi C et al (2005) Increased inflammation in mice deficient for the chemokine decoy receptor D6. Eur J Immunol 35:1342–1346

    CAS  PubMed  Google Scholar 

  62. Aswad M, Assi S, Schif-Zuck S, Ariel A (2017) CCL5 promotes resolution-phase macrophage reprogramming in concert with the atypical chemokine receptor D6 and apoptotic polymorphonuclear cells. J Immunol 199:1393–1404

    CAS  PubMed  Google Scholar 

  63. Lumbroso D, Soboh S, Maimon A, Schif-Zuck S, Ariel A, Burstyn-Cohen T (2018) Macrophage-derived protein S facilitates apoptotic polymorphonuclear cell clearance by resolution phase macrophages and supports their reprogramming. Front Immunol 9:358

    PubMed  PubMed Central  Google Scholar 

  64. Bornstein B, Gottfried Y, Edison N et al (2011) ARTS binds to a distinct domain in XIAP-BIR3 and promotes apoptosis by a mechanism that is different from other IAP-antagonists. Apoptosis 16:869–881

    CAS  PubMed  Google Scholar 

  65. Cash JL, White GE, Greaves DR (2009) Zymosan-induced peritonitis as a simple experimental system for the study of inflammation. Methods Enzymol 461:379–396

    CAS  PubMed  Google Scholar 

  66. Rostoker R, Yaseen H, Schif-Zuck S, Lichtenstein RG, Rabinovich GA, Ariel A (2013) Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors their conversion toward a pro-resolving phenotype. Prostaglandins Other Lipid Mediat 107:85–94

    CAS  PubMed  Google Scholar 

  67. Yang J, Zhang L, Yu C, Yang XF, Wang H (2014) Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark Res 2:1

    PubMed  PubMed Central  Google Scholar 

  68. Kolaczkowska E, Koziol A, Plytycz B, Arnold B (2010) Inflammatory macrophages, and not only neutrophils, die by apoptosis during acute peritonitis. Immunobiology 215:492–504

    CAS  PubMed  Google Scholar 

  69. Li P, Zhou L, Zhao T et al (2017) Caspase-9: structure, mechanisms and clinical application. Oncotarget 8:23996–24008

    PubMed  PubMed Central  Google Scholar 

  70. Plesca D, Mazumder S, Almasan A (2008) DNA damage response and apoptosis. Methods Enzymol 446:107–122

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Weinberg JB (2000) Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation. Immunol Res 22:319–341

    CAS  PubMed  Google Scholar 

  72. Vandooren J, Van den Steen PE, Opdenakker G (2013) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol 48:222–272

    CAS  PubMed  Google Scholar 

  73. Ackermann JA, Hofheinz K, Zaiss MM, Kronke G (2017) The double-edged role of 12/15-lipoxygenase during inflammation and immunity. Biochim Biophys Acta Mol Cell Biol Lipids 1862:371–381

    CAS  PubMed  Google Scholar 

  74. Xuan W, Qu Q, Zheng B, Xiong S, Fan GH (2015) The chemotaxis of M1 and M2 macrophages is regulated by different chemokines. J Leukoc Biol 97:61–69

    PubMed  Google Scholar 

  75. Huynh ML, Fadok VA, Henson PM (2002) Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest 109:41–50

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Bannenberg GL, Chiang N, Ariel A et al (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174:4345–4355

    CAS  PubMed  Google Scholar 

  77. McLoughlin RM, Witowski J, Robson RL et al (2003) Interplay between IFN-gamma and IL-6 signaling governs neutrophil trafficking and apoptosis during acute inflammation. J Clin Invest 112:598–607

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Filardy AA, Pires DR, Nunes MP et al (2010) Proinflammatory clearance of apoptotic neutrophils induces an IL-12(low)IL-10(high) regulatory phenotype in macrophages. J Immunol 185:2044–2050

    CAS  PubMed  Google Scholar 

  79. Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I (1997) Immunosuppressive effects of apoptotic cells. Nature 390:350–351

    CAS  PubMed  Google Scholar 

  80. Abdolmaleki F, Farahani N, Gheibi Hayat SM et al (2018) The Role of Efferocytosis in Autoimmune Diseases. Front Immunol 9:1645

    PubMed  PubMed Central  Google Scholar 

  81. Thomas D, Apovian C (2017) Macrophage functions in lean and obese adipose tissue. Metabolism 72:120–143

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Prame Kumar K, Nicholls AJ, Wong CHY (2018) Partners in crime: neutrophils and monocytes/macrophages in inflammation and disease. Cell Tissue Res 371:551–565

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Yurdagul A Jr, Doran AC, Cai B, Fredman G, Tabas IA (2017) Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis. Front Cardiovasc Med 4:86

    PubMed  Google Scholar 

  84. Grabiec AM, Hussell T (2016) The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation. Semin Immunopathol 38:409–423

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Kuhl AA, Erben U, Kredel LI, Siegmund B (2015) Diversity of Intestinal Macrophages in Inflammatory Bowel Diseases. Front Immunol 6:613

    PubMed  PubMed Central  Google Scholar 

  86. Lutaty A, Soboh S, Schif-Zuck S et al (2018) A 17-kDa Fragment of Lactoferrin Associates With the Termination of Inflammation and Peptides Within Promote Resolution. Front Immunol 9:644

    PubMed  PubMed Central  Google Scholar 

  87. Kumaran Satyanarayanan S, El Kebir D, Soboh S et al (2019) IFN-beta is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation. Nat Commun 10:3471

    PubMed  PubMed Central  Google Scholar 

  88. Villa A, Rizzi N, Vegeto E, Ciana P, Maggi A (2015) Estrogen accelerates the resolution of inflammation in macrophagic cells. Sci Rep 5:15224

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Rossi AG, Sawatzky DA, Walker A et al (2006) Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med 12:1056–1064

    CAS  PubMed  Google Scholar 

  90. McGrath EE, Marriott HM, Lawrie A et al (2011) TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. J Leukoc Biol 90:855–865

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Edison N, Reingewertz TH, Gottfried Y et al (2012) Peptides mimicking the unique ARTS-XIAP binding site promote apoptotic cell death in cultured cancer cells. Clin Cancer Res 18:2569–2578

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Kfir Lapid, Ph.D. (Berlin, Germany) for the professional manuscript writing and editing services. The study was supported by grants from the Israel Science Foundation (Grant No. 678/13 (to A.A) and 822/12 (to S.L), the Rosetetress Trust (to A.A) and The Wolsfon Charitable Trust (to A.A and to S.L), and by a generous grant award from the Hymen Milgrom Trust (to S.L). O.Z.T is a recipient of a presidential scholarship from the University of Haifa.

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  1. Naama Maimon, Zohar Zvi Zamir, and Prajakta Kalkar have contributed equally to this work.

Authors and Affiliations

  1. The Laboratory for molecular Pathways in the Resolution of Inflammation, Department of Human Biology and Medical Sciences, University of Haifa, 31905, Haifa, Israel

    Naama Maimon, Zohar Zvi Zamir, Prajakta Kalkar, Orly Zeytuni-Timor, Sagie Schif-Zuck & Amiram Ariel

  2. Cell Death and Cancer Research Laboratory, Department of Human Biology and Medical Sciences, University of Haifa, 31905, Haifa, Israel

    Naama Maimon, Orly Zeytuni-Timor & Sarit Larisch

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  1. Naama Maimon
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NM, ZZZ, PK, OZT, and SSZ performed experiments and analyzed the results. SSZ assisted in planning the experiments. SL and AA planned the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Sarit Larisch or Amiram Ariel.

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Maimon, N., Zamir, Z.Z., Kalkar, P. et al. The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation. Apoptosis 25, 558–573 (2020). https://doi.org/10.1007/s10495-020-01615-3

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