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Cited by 440Phagocytosis and Immune RegulationImmune Response and InflammationCell death mechanisms and regulation

Efferocytosis Signaling in the Regulation of Macrophage Inflammatory Responses

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Elliott, Michael R, Koster, Kyle M, Murphy, Patrick S·2017·The Journal of Immunology
DOI 10.4049/jimmunol.1601520PMC PMC5301545
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Abstract

Since the pioneering work of Elie Metchnikoff and the discovery of cellular immunity, the phagocytic clearance of cellular debris has been considered an integral component of resolving inflammation and restoring function of damaged and infected tissues. We now know that the phagocytic clearance of dying cells (efferocytosis), particularly by macrophages and other immune phagocytes, has profound consequences on innate and adaptive immune responses in inflamed tissues. These immunomodulatory effects result from an array of molecular signaling events between macrophages, dying cells, and other tissue-resident cells. In recent years, many of these molecular pathways have been identified and studied in the context of tissue inflammation, helping us better understand the relationship between efferocytosis and inflammation. We review specific types of efferocytosis-related signals that can impact macrophage immune responses and discuss their relevance to inflammation-related diseases.

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  • Efferocytosis does not culminate in antigen presentation and instead evokes a highly immune suppressive macrophage phenotype.

    “Efferocytosis does not culminate in antigen presentation and instead evokes a highly immune suppressive macrophage phenotype (35, 36).”

    From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [36]

    The Introduction’s “Cell death in inflamed tissues” section says apoptotic cells can suppress macrophage inflammatory responses and that efferocytosis promotes resolution, supporting the immunosuppressive aspect. The cited paper does not establish the separate, categorical claim that efferocytosis does not culminate in antigen presentation; searches for antigen presentation and related terms found no supporting passage in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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  1. [1]Headland SE Norling LV 2015 The resolution of inflammation: Principles and challenges Semin Immunol 27 149 160 25911383
  2. [2]Gilroy D De Maeyer R 2015 New insights into the resolution of inflammation Semin Immunol 27 161 168 26037968
  3. [3]Serhan CN 2014 Pro-resolving lipid mediators are leads for resolution physiology Nature 510 92 101 24899309 PMC4263681
  4. [4]Arandjelovic S Ravichandran KS 2015 Phagocytosis of apoptotic cells in homeostasis Nature Immunology 16 907 917 26287597 PMC4826466
  5. [7]Galluzzi L Bravo-San Pedro JM Vitale I Aaronson SA Abrams JM Adam D Alnemri ES Altucci L Andrews D Annicchiarico-Petruzzelli M Baehrecke EH Bazan NG Bertrand MJ Bianchi K Blagosklonny MV Blomgren K Borner C Bredesen DE Brenner C Campanella M Candi E Cecconi F Chan FK Chandel NS Cheng EH Chipuk JE Cidlowski JA Ciechanover A Dawson TM Dawson VL De Laurenzi V De Maria R Debatin KM Di Daniele N Dixit VM Dynlacht BD El-Deiry WS Fimia GM Flavell RA Fulda S Garrido C Gougeon M-L Green DR Gronemeyer H Hajnoczky G Hardwick JM Hengartner MO Ichijo H Joseph B Jost PJ Kaufmann T Kepp O Klionsky DJ Knight RA Kumar S Lemasters JJ Levine B Linkermann A Lipton SA Lockshin RA Lopez-Otin C Lugli E Madeo F Malorni W Marine J-C Martin SJ Martinou J-C Medema JP Meier P Melino S Mizushima N Moll U Muñoz-Pinedo C Nuñez G Oberst A Panaretakis T Penninger JM Peter ME Piacentini M Pinton P Prehn JH Puthalakath H Rabinovich GA Ravichandran KS Rizzuto R Rodrigues CM Rubinsztein DC Rudel T Shi Y Simon HU Stockwell BR Szabadkai G Tait SW Tang HL Tavernarakis N Tsujimoto Y Vanden Berghe T Vandenabeele P Villunger A Wagner EF Walczak H White E Wood WG Yuan J Zakeri Z Zhivotovsky B Melino G Kroemer G 2014 Essential versus accessory aspects of cell death: recommendations of the NCCD 2015 Cell Death Differ PMC4262782 25236395
  6. [8]Rock KL Kono H 2008 The inflammatory response to cell death Annu Rev Pathol 3 99 126 18039143 PMC3094097
  7. [9]Martin GS Mannino DM Moss M 2006 The effect of age on the development and outcome of adult sepsis Crit Care Med 34 15 21 16374151
  8. [11]Drewry Anne M NS LPS BMF SMC RSH 2014 Persistent Lymphopenia after Diagnosis of Sepsis Predicts Mortality Shock (Augusta, Ga) 42 383 PMC4362626 25051284
  9. [12]Hotchkiss RS Tinsley KW Swanson PE Chang KC Cobb JP Buchman TG Korsmeyer SJ Karl IE 1999 Prevention of lymphocyte cell death in sepsis improves survival in mice Proc Natl Acad Sci USA 96 14541 14546 10588741 PMC24472
  10. [13]Hotchkiss RS Swanson PE Knudson CM Chang KC Cobb JP Osborne DF Zollner KM Buchman TG Korsmeyer SJ Karl IE 1999 Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis J Immunol 162 4148 4156 10201940
  11. [14]Drifte G Dunn-Siegrist I Tissières P Pugin J 2013 Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome Crit Care Med 41 820 832 23348516
  12. [15]Adib-Conquy M Cavaillon JM 2009 Compensatory anti-inflammatory response syndrome Thromb Haemost 101 36 47 19132187
  13. [16]Fullerton JN O’Brien AJ Gilroy DW 2013 Pathways mediating resolution of inflammation: when enough is too much J Pathol 231 8 20 23794437
  14. [17]Fredman G Li Y Dalli J Chiang N Serhan CN 2012 Self-limited versus delayed resolution of acute inflammation: temporal regulation of pro-resolving mediators and microRNA Sci Rep 2 639 22957142 PMC3434392
  15. [19]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 22566890 PMC3342362
  16. [21]Bratton DL Henson PM 2011 Neutrophil clearance: when the party is over, clean-up begins Trends in Immunology 32 350 357 21782511 PMC3151332
  17. [22]Saas P Kaminski S Perruche S 2013 Prospects of apoptotic cell-based therapies for transplantation and inflammatory diseases Immunotherapy 5 1055 1073 24088076
  18. [23]Hochreiter-Hufford A Ravichandran KS 2013 Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion Cold Spring Harbor Perspectives in Biology 5 PMC3579390 23284042
  19. [24]Silva MT 2010 Secondary necrosis: The natural outcome of the complete apoptotic program FEBS Letters 584 4491 4499 20974143
  20. [25]Kono H Rock KL 2008 How dying cells alert the immune system to danger Nat Rev Immunol 8 279 289 18340345 PMC2763408
  21. [26]Elliott MR Ravichandran KS 2010 Clearance of apoptotic cells: implications in health and disease J Cell Biol 189 1059 1070 20584912 PMC2894449
  22. [27]Nagata S Hanayama R Kawane K 2010 Autoimmunity and the Clearance of Dead Cells Cell 140 619 630 20211132
  23. [28]Peter C Wesselborg S Herrmann M Lauber K 2010 Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells Apoptosis 15 1007 1028 20157780
  24. [29]Medina CB Ravichandran KS 2016 Do not let death do us part: “find-me” signals in communication between dying cells and the phagocytes Cell Death Differ PMC4987731 26891690
  25. [30]Elliott MR Chekeni FB Trampont PC Lazarowski ER Kadl A Walk SF Park D Woodson RI Ostankovich M Sharma P Lysiak JJ Harden TK Leitinger N Ravichandran KS 2009 Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance Nature 461 282 286 19741708 PMC2851546
  26. [31]Qu Y Misaghi S Newton K Gilmour LL Louie S Cupp JE Dubyak GR Hackos D Dixit VM 2011 Pannexin-1 Is Required for ATP Release during Apoptosis but Not for Inflammasome Activation The Journal of Immunology 186 6553 6561 21508259
  27. [32]Truman LA Ford CA Pasikowska M Pound JD Wilkinson SJ Dumitriu IE Melville L Melrose LA Ogden CA Nibbs R Graham G Combadiere C Gregory CD 2008 CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis Blood 112 5026 5036 18799722
  28. [34]Weigert A Johann AM von Knethen A Schmidt H Geisslinger G Brüne B 2006 Apoptotic cells promote macrophage survival by releasing the antiapoptotic mediator sphingosine-1-phosphate Blood 108 1635 1642 16690965
  29. [35]Gude DR Alvarez SE Paugh SW Mitra P Yu J Griffiths R Barbour SE Milstien S Spiegel S 2008 Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal The FASEB Journal 22 2629 2638 18362204 PMC2493451
  30. [36]Elliott MR Ravichandran KS 2016 The Dynamics of Apoptotic Cell Clearance Developmental Cell 38 147 160 27459067 PMC4966906
  31. [37]Chekeni FB Elliott MR Sandilos JK Walk SF Kinchen JM Lazarowski ER Armstrong AJ Penuela S Laird DW Salvesen GS Isakson BE Bayliss DA Ravichandran KS 2010 Pannexin 1 channels mediate “find-me” signal release and membrane permeability during apoptosis Nature 467 863 867 20944749 PMC3006164
  32. [38]Koizumi S Shigemoto-Mogami Y Nasu-Tada K Shinozaki Y Ohsawa K Tsuda M Joshi BV Jacobson KA Kohsaka S Inoue K 2007 UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis Nature 446 1091 1095 17410128 PMC3464483
  33. [39]Marques-da-Silva C Burnstock G Ojcius DM Coutinho-Silva R 2011 Purinergic receptor agonists modulate phagocytosis and clearance of apoptotic cells in macrophages Immunobiology 216 1 11 20471713
  34. [40]Frey B Rubner Y Kulzer L Werthmöller N Weiss EM Fietkau R Gaipl US 2013 Antitumor immune responses induced by ionizing irradiation and further immune stimulation Cancer Immunol Immunother 63 29 36 24052136 PMC11028436
  35. [41]Idzko M Ferrari D Eltzschig HK 2014 Nucleotide signalling during inflammation Nature 509 310 317 24828189 PMC4222675
  36. [42]Cekic C Linden J 2016 Purinergic regulation of the immune system Nat Rev Immunol 16 177 192 26922909
  37. [43]Koroskenyi K Duro E Pallai A Sarang Z Kloor D Ucker DS Beceiro S Castrillo A Chawla A Ledent CA Fesus L Szondy Z 2011 Involvement of Adenosine A2A Receptors in Engulfment-Dependent Apoptotic Cell Suppression of Inflammation The Journal of Immunology PMC3395167 21593381
  38. [44]Yamaguchi H Maruyama T Urade Y Nagata S 2014 Immunosuppression via adenosine receptor activation by adenosine monophosphate released from apoptotic cells Elife 3 e02172 24668173 PMC3963506
  39. [45]Cohen HB Briggs KT Marino JP Ravid K Robson SC Mosser DM 2013 TLR stimulation initiates a CD39-based autoregulatory mechanism that limits macrophage inflammatory responses Blood 122 1935 1945 23908469 PMC3772500
  40. [46]Sokolowski JD Mandell JW 2011 Phagocytic Clearance in Neurodegeneration AJPA 178 1416 1428 PMC3078427 21435432
  41. [47]Miksa M Amin D Wu R Ravikumar TS Wang P 2007 Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages Mol Med 13 553 560 17673941 PMC1936982
  42. [48]Fuller AD Van Eldik LJ 2008 MFG-E8 regulates microglial phagocytosis of apoptotic neurons J Neuroimmune Pharmacol 3 246 256 18670887 PMC2832904
  43. [49]Noda M Doi Y Liang J Kawanokuchi J Sonobe Y Takeuchi H Mizuno T Suzumura A 2011 Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression Journal of Biological Chemistry 286 2308 2319 21071446 PMC3023525
  44. [50]White GE Tan TCC John AE Whatling C McPheat WL Greaves DR 2010 Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signalling Cardiovasc Res 85 825 835 19840952 PMC2819832
  45. [51]Engel DR Krause TA Snelgrove SL Thiebes S Hickey MJ Boor P Kitching AR Kurts C 2015 CX3CR1 reduces kidney fibrosis by inhibiting local proliferation of profibrotic macrophages The Journal of Immunology 194 1628 1638 25595779
  46. [52]Weigert A Weis N Brüne B 2009 Regulation of macrophage function by sphingosine-1-phosphate Immunobiology 214 748 760 19625101
  47. [53]Weigert A Tzieply N von Knethen A Johann AM Schmidt H Geisslinger G Brüne B 2007 Tumor cell apoptosis polarizes macrophages role of sphingosine-1-phosphate Mol Biol Cell 18 3810 3819 17652460 PMC1995721
  48. [54]Weis N Weigert A von Knethen A Brüne B 2009 Heme oxygenase-1 contributes to an alternative macrophage activation profile induced by apoptotic cell supernatants Mol Biol Cell 20 1280 1288 19129475 PMC2649271
  49. [55]Johann AM Weigert A Eberhardt W Kuhn AM Barra V von Knethen A Pfeilschifter JM Brüne B 2008 Apoptotic cell-derived sphingosine-1-phosphate promotes HuR-dependent cyclooxygenase-2 mRNA stabilization and protein expression J Immunol 180 1239 1248 18178864
  50. [56]Luo B Gan W Liu Z Shen Z Wang J Shi R Liu Y Liu Y Jiang M Zhang Z Wu Y 2016 Erythropoeitin Signaling in Macrophages Promotes Dying Cell Clearance and Immune Tolerance Immunity 44 287 302 26872696
  51. [59]Segawa K Nagata S 2015 An Apoptotic “Eat Me” Signal: Phosphatidylserine Exposure Trends Cell Biol 26437594
  52. [60]Penberthy KK Ravichandran KS 2015 Apoptotic cell recognition receptors and scavenger receptors Immunol Rev 269 44 59 PMC4685734 26683144
  53. [61]Huynh ML V Fadok A Henson PM 2002 Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation Journal of Clinical Investigation 109 41 50 11781349 PMC150814
  54. [62]Park D Tosello-Trampont AC Elliott MR Lu M Haney LB Ma Z Klibanov AL Mandell JW Ravichandran KS 2007 BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module Nature 450 430 434 17960134
  55. [63]Das S Sarkar A Ryan KA Fox S Berger AH Juncadella IJ Bimczok D Smythies LE Harris PR Ravichandran KS Crowe SE Smith PD Ernst PB 2014 Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells The FASEB Journal PMC3986834 24509909
  56. [64]Lee CS Penberthy KK Wheeler KM Juncadella IJ Vandenabeele P Lysiak JJ Ravichandran KS 2016 Boosting Apoptotic Cell Clearance by Colonic Epithelial Cells Attenuates Inflammation In Vivo Immunity PMC4838559 27037190
  57. [65]Shimazaki A Kawamura Y Kanazawa A Sekine A Saito S Tsunoda T Koya D Babazono T Tanaka Y Matsuda M Kawai K Iiizumi T Imanishi M Shinosaki T Yanagimoto T Ikeda M Omachi S Kashiwagi A Kaku K Iwamoto Y Kawamori R Kikkawa R Nakajima M Nakamura Y Maeda S 2005 Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy Diabetes 54 1171 1178 15793258
  58. [66]Mauldin JP Lu M Das S Park D Ernst PB Ravichandran KS 2012 A Link between the Cytoplasmic Engulfment Protein Elmo1 and the Mediator Complex Subunit Med31 Curr Biol PMC3556191 23273896
  59. [67]Zhang B Shi L Lu S Sun X Liu Y Li H Wang X Zhao C Zhang H Wang Y 2015 Autocrine IL-8 promotes F-actin polymerization and mediate mesenchymal transition via ELMO1-NF-κB-Snail signaling in glioma Cancer Biol Ther 16 898 911 25870011 PMC4623112
  60. [68]Yin J Haney L Walk S Zhou S Ravichandran KS Wang W 2004 Nuclear localization of the DOCK180/ELMO complex Archives of Biochemistry and Biophysics 429 23 29 15288806
  61. [69]Kobayashi N Karisola P Peña-Cruz V Dorfman DM Jinushi M Umetsu SE Butte MJ Nagumo H Chernova I Zhu B Sharpe AH Ito S Dranoff G Kaplan GG Casasnovas JM Umetsu DT DeKruyff RH Freeman GJ 2007 TIM-1 and TIM-4 Glycoproteins Bind Phosphatidylserine and Mediate Uptake of Apoptotic Cells Immunity 27 927 940 18082433 PMC2757006
  62. [70]Freeman GJ Casasnovas JM Umetsu DT DeKruyff RH 2010 TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity Immunol Rev 235 172 189 20536563 PMC2914464
  63. [71]Miyanishi M Tada K Koike M Uchiyama Y Kitamura T Nagata S 2007 Identification of Tim4 as a phosphatidylserine receptor Nature 450 435 439 17960135
  64. [72]Baghdadi M Jinushi M 2014 The impact of the TIM gene family on tumor immunity and immunosuppression Cell Mol Immunol 11 41 48 24336162 PMC4002149
  65. [73]Wong K Valdez PA Tan C Yeh S Hongo JA Ouyang W 2010 Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages Proceedings of the National Academy of Sciences 107 8712 8717 PMC2889355 20421466
  66. [74]Rodriguez-Manzanet R Sanjuan MA Wu HY Quintana FJ Xiao S Anderson AC Weiner HL Green DR Kuchroo VK 2010 T and B cell hyperactivity and autoimmunity associated with niche-specific defects in apoptotic body clearance in TIM-4-deficient mice Proceedings of the National Academy of Sciences 107 8706 8711 PMC2889349 20368430
  67. [75]Thornley TB Fang Z Balasubramanian S Larocca RA Gong W Gupta S Csizmadia E Degauque N Kim BS Koulmanda M Kuchroo VK Strom TB 2014 Fragile TIM-4-expressing tissue resident macrophages are migratory and immunoregulatory Journal of Clinical Investigation 124 3443 3454 24983317 PMC4109530
  68. [76]Ichimura T Asseldonk EJPV Humphreys BD Gunaratnam L Duffield JS Bonventre JV 2008 Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells Journal of Clinical Investigation 118 1657 1668 18414680 PMC2293335
  69. [77]Yang L Brooks CR Xiao S Sabbisetti V Yeung MY Hsiao LL Ichimura T Kuchroo V Bonventre JV 2015 KIM-1–mediated phagocytosis reduces acute injury to the kidney Journal of Clinical Investigation 125 1620 1636 25751064 PMC4396492
  70. [78]Ocaña-Guzman R Torre-Bouscoulet L Sada-Ovalle I 2016 TIM-3 Regulates Distinct Functions in Macrophages Front Immunol 7 229 27379093 PMC4904032
  71. [79]Nakayama M Akiba H Takeda K Kojima Y Hashiguchi M Azuma M Yagita H Okumura K 2009 Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation Blood 113 3821 3830 19224762
  72. [80]Park D Hochreiter-Hufford A Ravichandran KS 2009 The phosphatidylserine receptor TIM-4 does not mediate direct signaling Curr Biol 19 346 351 19217291
  73. [81]Dransfield I Zagórska A Lew ED Michail K Lemke G 2015 Mer receptor tyrosine kinase mediates both tethering and phagocytosis of apoptotic cells Cell Death and Disease 6 e1646 25695599 PMC4669813
  74. [84]Voss OH Tian L Murakami Y Coligan JE Krzewski K 2015 Emerging role of CD300 receptors in regulating myeloid cell efferocytosis Mol Cell Oncol 2 e964625 27308512 PMC4905414
  75. [85]Simhadri VR Andersen JF Calvo E Choi S-C Coligan JE Borrego F 2012 Human CD300a binds to phosphatidylethanolamine and phosphatidylserine and modulates the phagocytosis of dead cells Blood PMC3327458 22302738
  76. [86]Nakahashi-Oda C Tahara-Hanaoka S Shoji M Okoshi Y Nakano-Yokomizo T Ohkohchi N Yasui T Kikutani H Honda SI Shibuya K Nagata S Shibuya A 2012 Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor Journal of Experimental Medicine 209 1493 1503 22826299 PMC3409498
  77. [87]Tian L Choi SC Murakami Y Allen J Morse HC Qi CF Krzewski K Coligan JE 2014 p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression Nat Commun 5 3146 24477292 PMC4151829
  78. [88]Voss OH Murakami Y Pena MY Lee HN Tian L Margulies DH Street JM Yuen PST Qi CF Krzewski K Coligan JE 2016 Lipopolysaccharide-Induced CD300b Receptor Binding to Toll-like Receptor 4 Alters Signaling to Drive Cytokine Responses that Enhance Septic Shock Immunity 44 1365 1378 27261276 PMC4917413
  79. [89]Moshkovits I Karo-Atar D Itan M Reichman H Rozenberg P Morgenstern-Ben-Baruch N Shik D Ejarque-Ortiz A Hershko AY Tian L Coligan JE Sayós J Munitz A 2015 CD300f associates with IL-4 receptor α and amplifies IL-4-induced immune cell responses Proc Natl Acad Sci USA 112 8708 8713 26124135 PMC4507247
  80. [90]Kzhyshkowska J Gratchev A Goerdt S 2006 Stabilin-1, a homeostatic scavenger receptor with multiple functions J Cell Mol Med 10 635 649 16989725 PMC3933147
  81. [91]Park SY Jung MY Kim HJ Lee SJ Kim SY Lee BH Kwon TH Park RW Kim IS 2007 Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor Cell Death Differ 15 192 201 17962816
  82. [92]Park SY Jung MY Lee SJ Kang KB Gratchev A Riabov V Kzhyshkowska J Kim IS 2009 Stabilin-1 mediates phosphatidylserine-dependent clearance of cell corpses in alternatively activated macrophages J Cell Sci 122 3365 3373 19726632
  83. [94]Kzhyshkowska J 2010 Multifunctional receptor stabilin-1 in homeostasis and disease Scientific World Journal 10 2039 2053 20953554 PMC5763786
  84. [95]Hirose Y Saijou E Sugano Y Takeshita F Nishimura S Nonaka H Chen YR Sekine K Kido T Nakamura T Kato S Kanke T Nakamura K Nagai R Ochiya T Miyajima A 2012 Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis Proc Natl Acad Sci USA 109 4263 4268 22371575 PMC3306694
  85. [96]Schledzewski K Géraud C Arnold B Wang S Gröne HJ Kempf T Wollert KC Straub BK Schirmacher P Demory A Schönhaber H Gratchev A Dietz L Thierse HJ Kzhyshkowska J Goerdt S 2011 Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors Journal of Clinical Investigation 121 703 714 21293057 PMC3026735
  86. [97]Park SY Kim SY Kang KB Kim IS 2010 Adaptor protein GULP is involved in stabilin-1-mediated phagocytosis Biochemical and Biophysical Research Communications 398 467 472 20599701
  87. [98]Ma CIJ Martin C Ma Z Hafiane A Dai M Lebrun JJ Kiss RS 2012 Engulfment protein GULP is regulator of transforming growth factor-β response in ovarian cells Journal of Biological Chemistry 287 20636 20651 22451657 PMC3370247
  88. [101]Lacy-Hulbert A Smith AM Tissire H Barry M Crowley D Bronson RT Roes JT Savill JS Hynes RO 2007 Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins Proc Natl Acad Sci USA 104 15823 15828 17895374 PMC1994135
  89. [102]Asano K Miwa M Miwa K Hanayama R Nagase H Nagata S Tanaka M 2004 Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice J Exp Med 200 459 467 15302904 PMC2211927
  90. [103]Schutters K Kusters DHM Chatrou MLL Montero-Melendez T Donners M Deckers NM Krysko DV Vandenabeele P Perretti M Schurgers LJ Reutelingsperger CPM 2012 Cell surface-expressed phosphatidylserine as therapeutic target to enhance phagocytosis of apoptotic cells Cell Death Differ PMC3524641 22955945
  91. [104]Voll RE Herrmann M Roth EA Stach C Kalden JR Girkontaite I 1997 Immunosuppressive effects of apoptotic cells Nature 390 350 351 9389474
  92. [105]Lucas M Stuart LM Zhang A Hodivala-Dilke K Febbraio M Silverstein R Savill J Lacy-Hulbert A 2006 Requirements for apoptotic cell contact in regulation of macrophage responses J Immunol 177 4047 4054 16951368
  93. [106]Savill J Hogg N Ren Y Haslett C 1992 Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis Journal of Clinical Investigation 90 1513 1522 1383273 PMC443198
  94. [107]Friggeri A Yang Y Banerjee S Park YJ Liu G Abraham E 2010 HMGB1 inhibits macrophage activity in efferocytosis through binding to the v 3-integrin AJP: Cell Physiology 299 C1267 C1276 20826760 PMC3006331
  95. [109]Seitz HM Camenisch TD Lemke G Earp HS Matsushima GK 2007 Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells J Immunol 178 5635 5642 17442946
  96. [110]Sharif MN Šošić D Rothlin CV Kelly E Lemke G Olson EN Ivashkiv LB 2006 Twist mediates suppression of inflammation by type I IFNs and Axl J Exp Med 203 1891 1901 16831897 PMC2118370
  97. [111]Rothlin CV Ghosh S Zuniga EI Oldstone MBA Lemke G 2007 TAM receptors are pleiotropic inhibitors of the innate immune response Cell 131 1124 1136 18083102
  98. [113]Sen P Wallet MA Yi Z Huang Y Henderson M Mathews CE Earp HS Matsushima G Baldwin AS Tisch RM 2007 Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF- B activation in dendritic cells Blood 109 653 660 17008547 PMC1785106
  99. [114]Han CZ Ravichandran KS 2011 Metabolic Connections during Apoptotic Cell Engulfment Cell 147 1442 1445 22196723 PMC3254670
  100. [115]Kiss RS Elliott MR Ma Z Marcel YL Ravichandran KS 2006 Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes Curr Biol 16 2252 2258 17113390
  101. [116]Hsu CL Lin W Seshasayee D Chen YH Ding X Lin Z Suto E Huang Z Lee WP Park H Xu M Sun M Rangell L Lutman JL Ulufatu S Stefanich E Chalouni C Sagolla M Diehl L Fielder P Dean B Balazs M Martin F 2011 Equilibrative Nucleoside Transporter 3 Deficiency Perturbs Lysosome Function and Macrophage Homeostasis Science 22174130
  102. [118]Park D Han CZ Elliott MR Kinchen JM Trampont PC Das S Collins S Lysiak JJ Hoehn KL Ravichandran KS 2011 Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein Nature 1 7 PMC3513690 21857682
  103. [119]A-Gonzalez N Castrillo A 2011 Liver X receptors as regulators of macrophage inflammatory and metabolic pathways BBA - Molecular Basis of Disease 1812 982 994 21193033
  104. [121]A-Gonzalez N Bensinger SJ Hong C Beceiro S Bradley MN Zelcer N Deniz J Ramirez C DIaz M Gallardo G de Galarreta CR Salazar J Lopez F Edwards P Parks J Andujar M Tontonoz P Castrillo A 2009 Apoptotic Cells Promote Their Own Clearance and Immune Tolerance through Activation of the Nuclear Receptor LXR Immunity 1 14 PMC2791787 19646905
  105. [122]Roszer T Menéndez-Gutiérrez MP Lefterova MI Alameda D Núñez V Lazar MA Fischer T Ricote M 2011 Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha deficiency The Journal of Immunology 186 621 631 21135166 PMC4038038
  106. [123]Ipseiz N Uderhardt S Scholtysek C Steffen M Schabbauer G Bozec A Schett G Krönke G 2014 The Nuclear Receptor Nr4a1 Mediates Anti-Inflammatory Effects of Apoptotic Cells The Journal of Immunology 24740500
  107. [124]Crean D Cummins EP Bahar B Mohan H McMorrow JP Murphy EP 2015 Adenosine Modulates NR4A Orphan Nuclear Receptors To Attenuate Hyperinflammatory Responses in Monocytic Cells The Journal of Immunology 195 1436 1448 26150530
  108. [125]Birge RB Boeltz S Kumar S Carlson J Wanderley J Calianese D Barcinski M Brekken RA Huang X Hutchins JT Freimark B Empig C Mercer J Schroit AJ Schett G Herrmann M 2016 Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer Cell Death Differ 23 962 978 26915293 PMC4987730
  109. [126]Saas P Daguindau E Perruche S 2016 Concise Review: Apoptotic Cell-Based Therapies -Rationale, Preclinical Results and Future Clinical Developments Stem Cells 27018198

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Authors
Elliott, M. R., Koster, K. M., & Murphy, P. S.
Affiliations
University of Rochester Medicine (US)
Corresponding author
Elliott, Michael R
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2017-02
Volume
198
Issue
4
Pages
1387-1394
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1601520
PMC
PMC5301545
OpenAlex
W2755895700
Cited by
440
References
17
Citations by year
2026: 39 · 2025: 44 · 2024: 67 · 2023: 51 · 2022: 65 · 2021: 56 · 2020: 53 · 2019: 35 · 2018: 25 · 2017: 4 · 2014: 1
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of General Medical Sciences (T32GM007356)
  • National Institute of Allergy and Infectious Diseases (R01AI114554, T32AI007285)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
efferocytosis, macrophages, inflammation resolution, immunomodulation, innate immunity, adaptive immunity, tissue inflammation, inflammation-related diseases, signaling pathways
MeSH terms
Animals, Cells, Cultured, Humans, Immunity, Innate, Inflammation, Macrophages, Phagocytes, Phagocytosis, Signal Transduction, Apoptosis, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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