CoChat
Sign Up
Cited by 959Phagocytosis and Immune RegulationCell death mechanisms and regulationAutophagy in Disease and Therapy

Phagocytosis of apoptotic cells in homeostasis

Open access
Arandjelovic, Sanja, Ravichandran, Kodi S·2015·Nature Immunology
DOI 10.1038/ni.3253PMC PMC4826466
Open this paper in CoChat — free accountOpen PDF

Abstract

Human bodies collectively turn over about 200 billion to 300 billion cells every day. Such turnover is an integral part of embryonic and postnatal development, as well as routine tissue homeostasis. This process involves the induction of programmed cell death in specific cells within the tissues and the specific recognition and removal of dying cells by a clearance 'crew' composed of professional, non-professional and specialized phagocytes. In the past few years, considerable progress has been made in identifying many features of apoptotic cell clearance. Some of these new observations challenge the way dying cells themselves are viewed, as well as how healthy cells interact with and respond to dying cells. Here we focus on the homeostatic removal of apoptotic cells in tissues.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/ni.3253

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Many cell types are capable of slowly engulfing injured/dead cells in their close proximity.

    “Many cell types are indeed capable of slowly engulfing the injured/dead cell in their close proximity22.”

    From Hepatocyte mitochondria-derived danger signals directly activate hepatic stellate cells and drive progression of liver fibrosis (2020) · cites this paper as [22]

    The ‘Phagocyte types and the tissue contexts’ section says that professional and non-professional phagocytes can clear apoptotic cells, including neighboring epithelial cells. It describes non-professional phagocytes as less efficient, but does not establish that engulfment is generally slow or extend the finding to injured cells that are not apoptotic. No page number is available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Apoptotic bodies are selectively ingested by phagocytic cells to avoid local release of cell contents and related local inflammation.

    “The apoptotic bodies are further selectively ingested by phagocytic cells to avoid local release of cell contents and related local inflammation [21,22,23].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [21]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 143

  1. [1]Nagata S Hanayama R Kawane K Autoimmunity and the clearance of dead cells Cell 140 619 630 2010 20211132
  2. [3]Monks J Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release Cell death and differentiation 12 107 114 2005 15647754
  3. [4]Nagata S Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors Immunological reviews 220 237 250 2007 17979851
  4. [6]van Furth R The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells Bulletin of the World Health Organization 46 845 852 1972 4538544 PMC2480884
  5. [7]Lavin Y Merad M Macrophages: gatekeepers of tissue integrity Cancer immunology research 1 201 209 2013 24777851 PMC4144820
  6. [11]Dini L Pagliara P Carla EC Phagocytosis of apoptotic cells by liver: a morphological study Microscopy research and technique 57 530 540 2002 12112436
  7. [12]Bilimoria PM Stevens B Microglia function during brain development: New insights from animal models Brain research 2014 25463024
  8. [13]Uderhardt S 12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance Immunity 36 834 846 2012 22503541
  9. [14]Wood W Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos Development 127 5245 5252 2000 11076747
  10. [15]Juncadella IJ Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation Nature 493 547 551 2013 23235830 PMC3662023
  11. [16]Elliott MR Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo Nature 467 333 337 2010 20844538 PMC3773546
  12. [17]Lysiak JJ Turner SD Turner TT Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis Biology of reproduction 63 1465 1472 2000 11058553
  13. [19]Elliott MR Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance Nature 461 282 286 2009 19741708 PMC2851546
  14. [20]Gude DR Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal FASEB journal: official publication of the Federation of American Societies for Experimental Biology 22 2629 2638 2008 18362204 PMC2493451
  15. [22]Peter C Wesselborg S Herrmann M Lauber K Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells Apoptosis: an international journal on programmed cell death 15 1007 1028 2010 20157780
  16. [23]Truman LA CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis Blood 112 5026 5036 2008 18799722
  17. [24]Miksa M Amin D Wu R Ravikumar TS Wang P Fractalkine-induced MFG-E8 leads to enhanced apoptotic cell clearance by macrophages Mol Med 13 553 560 2007 17673941 PMC1936982
  18. [25]Darland-Ransom M Role of C. elegans TAT-1 protein in maintaining plasma membrane phosphatidylserine asymmetry Science 320 528 531 2008 18436785
  19. [26]Fadok VA Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages J Immunol 148 2207 2216 1992 1545126
  20. [27]Balasubramanian K Schroit AJ Aminophospholipid asymmetry: A matter of life and death Annual review of physiology 65 701 734 2003 12471163
  21. [28]Suzuki J Denning DP Imanishi E Horvitz HR Nagata S Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells Science 341 403 406 2013 23845944
  22. [29]Segawa K Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure Science 344 1164 1168 2014 24904167
  23. [30]Suzuki J Umeda M Sims PJ Nagata S Calcium-dependent phospholipid scrambling by TMEM16F Nature 468 834 838 2010 21107324
  24. [31]Lauber K Blumenthal SG Waibel M Wesselborg S Clearance of apoptotic cells: getting rid of the corpses Molecular cell 14 277 287 2004 15125832
  25. [33]Simhadri VR Human CD300a binds to phosphatidylethanolamine and phosphatidylserine, and modulates the phagocytosis of dead cells Blood 119 2799 2809 2012 22302738 PMC3327458
  26. [35]Hamann J International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors Pharmacological reviews 67 338 367 2015 25713288 PMC4394687
  27. [36]Duman JG The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites The Journal of neuroscience: the official journal of the Society for Neuroscience 33 6964 6978 2013 23595754 PMC3670686
  28. [37]Hochreiter-Hufford AE Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion Nature 497 263 267 2013 23615608 PMC3773542
  29. [38]Kaur B Brat DJ Devi NS Van Meir EG Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor Oncogene 24 3632 3642 2005 15782143
  30. [39]Park D BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module Nature 450 430 434 2007 17960134
  31. [40]Zhu D BAI1 regulates spatial learning and synaptic plasticity in the hippocampus The Journal of clinical investigation 125 1497 1508 2015 25751059 PMC4396478
  32. [42]Freeman GJ Casasnovas JM Umetsu DT DeKruyff RH TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity Immunological reviews 235 172 189 2010 20536563 PMC2914464
  33. [43]Miyanishi M Identification of Tim4 as a phosphatidylserine receptor Nature 450 435 439 2007 17960135
  34. [44]Kobayashi N TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells Immunity 27 927 940 2007 18082433 PMC2757006
  35. [45]Park D Hochreiter-Hufford A Ravichandran KS The phosphatidylserine receptor TIM-4 does not mediate direct signaling Current biology: CB 19 346 351 2009 19217291
  36. [46]Flannagan RS Canton J Furuya W Glogauer M Grinstein S The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis Molecular biology of the cell 25 1511 1522 2014 24623723 PMC4004599
  37. [47]Mazaheri F Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia Nature communications 5 4046 2014 24898390
  38. [48]Rodriguez-Manzanet R 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 of the United States of America 107 8706 8711 2010 20368430 PMC2889349
  39. [49]Wong K Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages Proceedings of the National Academy of Sciences of the United States of America 107 8712 8717 2010 20421466 PMC2889355
  40. [50]Miyanishi M Segawa K Nagata S Synergistic effect of Tim4 and MFG-E8 null mutations on the development of autoimmunity International immunology 24 551 559 2012 22723547
  41. [51]Albacker LA TIM-4, a receptor for phosphatidylserine, controls adaptive immunity by regulating the removal of antigen-specific T cells J Immunol 185 6839 6849 2010 21037090 PMC3153437
  42. [53]Lew ED Differential TAM receptor-ligand-phospholipid interactions delimit differential TAM bioactivities eLife 3 2014 PMC4206827 25265470
  43. [54]Zagorska A Traves PG Lew ED Dransfield I Lemke G Diversification of TAM receptor tyrosine kinase function Nature immunology 15 920 928 2014 25194421 PMC4169336
  44. [57]Duncan JL An RCS-like retinal dystrophy phenotype in mer knockout mice Investigative ophthalmology & visual science 44 826 838 2003 12556419
  45. [58]Rothlin CV Ghosh S Zuniga EI Oldstone MB Lemke G TAM receptors are pleiotropic inhibitors of the innate immune response Cell 131 1124 1136 2007 18083102
  46. [60]N AG Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR Immunity 31 245 258 2009 19646905 PMC2791787
  47. [61]Roszer T Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha deficiency J Immunol 186 621 631 2011 21135166 PMC4038038
  48. [62]Park D Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein Nature 477 220 224 2011 21857682 PMC3513690
  49. [63]Yoshida H Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells Nature 437 754 758 2005 16193055
  50. [64]Toda S Segawa K Nagata S MerTK-mediated engulfment of pyrenocytes by central macrophages in erythroblastic islands Blood 123 3963 3971 2014 24659633
  51. [65]Kawane K Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver Science 292 1546 1549 2001 11375492
  52. [66]Yoshida H Okabe Y Kawane K Fukuyama H Nagata S Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA Nature immunology 6 49 56 2005 15568025
  53. [67]Kawane K Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages Nature 443 998 1002 2006 17066036
  54. [68]Marcel YL Ouimet M Wang MD Regulation of cholesterol efflux from macrophages Current opinion in lipidology 19 455 461 2008 18769226
  55. [69]Oram JF Heinecke JW ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease Physiological reviews 85 1343 1372 2005 16183915
  56. [70]Kiss RS Elliott MR Ma Z Marcel YL Ravichandran KS Apoptotic cells induce a phosphatidylserine-dependent homeostatic response from phagocytes Current biology: CB 16 2252 2258 2006 17113390
  57. [71]Janko C CRP/anti-CRP antibodies assembly on the surfaces of cell remnants switches their phagocytic clearance toward inflammation Frontiers in immunology 2 70 2011 22566859 PMC3341995
  58. [72]Poon IK Hulett MD Parish CR Molecular mechanisms of late apoptotic/necrotic cell clearance Cell death and differentiation 17 381 397 2010 20019744
  59. [73]Zhang Y Brenner M Yang WL Wang P Recombinant human MFG-E8 ameliorates colon damage in DSS- and TNBS-induced colitis in mice Laboratory investigation; a journal of technical methods and pathology 95 480 490 2015 25751740
  60. [74]Gatza E Extracorporeal photopheresis reverses experimental graft-versus-host disease through regulatory T cells Blood 112 1515 1521 2008 18411417 PMC2515148
  61. [75]Pasparakis M Vandenabeele P Necroptosis and its role in inflammation Nature 517 311 320 2015 25592536
  62. [76]Remijsen Q Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality Cell death and differentiation 18 581 588 2011 21293492 PMC3131909
  63. [77]Schauer C Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines Nature medicine 20 511 517 2014 24784231
  64. [78]Fan Y Bergmann A Apoptosis-induced compensatory proliferation. The Cell is dead. Long live the Cell! Trends in cell biology 18 467 473 2008 18774295 PMC2705980
  65. [79]Chera S Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration Developmental cell 17 279 289 2009 19686688
  66. [80]Tseng AS Adams DS Qiu D Koustubhan P Levin M Apoptosis is required during early stages of tail regeneration in Xenopus laevis Developmental biology 301 62 69 2007 17150209 PMC3136124
  67. [82]Vlaskalin T Wong CJ Tsilfidis C Growth and apoptosis during larval forelimb development and adult forelimb regeneration in the newt (Notophthalmus viridescens) Development genes and evolution 214 423 431 2004 15322877
  68. [83]Li F Apoptotic cells activate the “phoenix rising” pathway to promote wound healing and tissue regeneration Science signaling 3 ra13 2010 20179271 PMC2905599
  69. [84]Rongvaux A Apoptotic caspases prevent the induction of type I interferons by mitochondrial DNA Cell 159 1563 1577 2014 25525875 PMC4272443
  70. [85]Ravichandran KS Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums The Journal of experimental medicine 207 1807 1817 2010 20805564 PMC2931173
  71. [86]Elliott JI Membrane phosphatidylserine distribution as a non-apoptotic signalling mechanism in lymphocytes Nature cell biology 7 808 816 2005 16025105
  72. [87]Carrera Silva EA T cell-derived protein S engages TAM receptor signaling in dendritic cells to control the magnitude of the immune response Immunity 39 160 170 2013 23850380 PMC4017237
  73. [88]Martin S Immunologic stimulation of mast cells leads to the reversible exposure of phosphatidylserine in the absence of apoptosis International archives of allergy and immunology 123 249 258 2000 11112862
  74. [89]Frasch SC Phospholipid flip-flop and phospholipid scramblase 1 (PLSCR1) co-localize to uropod rafts in formylated Met-Leu-Phe-stimulated neutrophils The Journal of biological chemistry 279 17625 17633 2004 14766753
  75. [90]van den Eijnde SM Transient expression of phosphatidylserine at cell-cell contact areas is required for myotube formation Journal of cell science 114 3631 3642 2001 11707515
  76. [91]Hamoud N Tran V Croteau LP Kania A Cote JF G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates Proceedings of the National Academy of Sciences of the United States of America 111 3745 3750 2014 24567399 PMC3956190
  77. [92]Wanderley JL Moreira ME Benjamin A Bonomo AC Barcinski MA Mimicry of apoptotic cells by exposing phosphatidylserine participates in the establishment of amastigotes of Leishmania (L) amazonensis in mammalian hosts J Immunol 176 1834 1839 2006 16424214
  78. [93]Seabra SH de Souza W Damatta RA Toxoplasma gondii exposes phosphatidylserine inducing a TGF-beta1 autocrine effect orchestrating macrophage evasion Biochemical and biophysical research communications 324 744 752 2004 15474490
  79. [94]Damatta RA Trypanosoma cruzi exposes phosphatidylserine as an evasion mechanism FEMS microbiology letters 266 29 33 2007 17092297
  80. [95]Mercer J Helenius A Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells Science 320 531 535 2008 18436786
  81. [96]Callahan MK Phosphatidylserine on HIV envelope is a cofactor for infection of monocytic cells J Immunol 170 4840 4845 2003 12707367
  82. [97]Brindley MA Tyrosine kinase receptor Axl enhances entry of Zaire ebolavirus without direct interactions with the viral glycoprotein Virology 415 83 94 2011 21529875 PMC3107944
  83. [98]Hunt CL Kolokoltsov AA Davey RA Maury W The Tyro3 receptor kinase Axl enhances macropinocytosis of Zaire ebolavirus Journal of virology 85 334 347 2011 21047970 PMC3014168
  84. [99]Meertens L The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry Cell host & microbe 12 544 557 2012 23084921 PMC3572209
  85. [100]Morizono K Chen IS Role of phosphatidylserine receptors in enveloped virus infection Journal of virology 88 4275 4290 2014 24478428 PMC3993771
  86. [101]Chen YH Phosphatidylserine vesicles enable efficient en bloc transmission of enteroviruses Cell 160 619 630 2015 25679758 PMC6704014
  87. [102]Das S Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria Proceedings of the National Academy of Sciences of the United States of America 108 2136 2141 2011 21245295 PMC3033312
  88. [103]N’Diaye EN TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria The Journal of cell biology 184 215 223 2009 19171755 PMC2654305
  89. [104]Adachi H Tsujimoto M FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities The Journal of biological chemistry 277 34264 34270 2002 12077138
  90. [105]Means TK Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36 The Journal of experimental medicine 206 637 653 2009 19237602 PMC2699123
  91. [106]Henson PM Dampening inflammation Nature immunology 6 1179 1181 2005 16369556
  92. [107]Colegio OR Functional polarization of tumour-associated macrophages by tumour-derived lactic acid Nature 513 559 563 2014 25043024 PMC4301845
  93. [109]Gaultier A Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis Journal of cell science 122 1155 1162 2009 19299462 PMC2714439
  94. [110]Tasdemir-Yilmaz OE Freeman MR Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons Genes & development 28 20 33 2014 24361692 PMC3894410
  95. [111]Lu Z Phagocytic activity of neuronal progenitors regulates adult neurogenesis Nature cell biology 13 1076 1083 2011 21804544 PMC3374401
  96. [112]Garcia M Vecino E Role of Muller glia in neuroprotection and regeneration in the retina Histology and histopathology 18 1205 1218 2003 12973689
  97. [114]Wu Y Singh S Georgescu MM Birge RB A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells Journal of cell science 118 539 553 2005 15673687
  98. [115]Todt JC Hu B Curtis JL The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages Journal of leukocyte biology 75 705 713 2004 14704368 PMC2441598
  99. [116]Ji H T-cell immunoglobulin and mucin domain 4 (TIM-4) signaling in innate immune-mediated liver ischemia-reperfusion injury Hepatology 60 2052 2064 2014 25066922 PMC4396987
  100. [117]Karikoski M Clever-1/stabilin-1 controls cancer growth and metastasis Clinical cancer research: an official journal of the American Association for Cancer Research 20 6452 6464 2014 25320356
  101. [118]Hirose Y Inhibition of Stabilin-2 elevates circulating hyaluronic acid levels and prevents tumor metastasis Proceedings of the National Academy of Sciences of the United States of America 109 4263 4268 2012 22371575 PMC3306694
  102. [119]Schledzewski K Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors The Journal of clinical investigation 121 703 714 2011 21293057 PMC3026735
  103. [120]Englert JM A role for the receptor for advanced glycation end products in idiopathic pulmonary fibrosis The American journal of pathology 172 583 591 2008 18245812 PMC2258251
  104. [121]Englert JM Paradoxical function for the receptor for advanced glycation end products in mouse models of pulmonary fibrosis International journal of clinical and experimental pathology 4 241 254 2011 21487520 PMC3071657
  105. [122]He M The role of the receptor for advanced glycation end-products in lung fibrosis American journal of physiology. Lung cellular and molecular physiology 293 L1427 1436 2007 17951314
  106. [123]He M Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells EMBO reports 12 358 364 2011 21399623 PMC3077249
  107. [124]Liliensiek B Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response The Journal of clinical investigation 113 1641 1650 2004 15173891 PMC419481
  108. [125]Tian L p85alpha recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression Nature communications 5 3146 2014 PMC4151829 24477292
  109. [129]Wang Y TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model Cell 160 1061 1071 2015 25728668 PMC4477963
  110. [130]Bosurgi L Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in colon cancer Proceedings of the National Academy of Sciences of the United States of America 110 13091 13096 2013 23878224 PMC3740859
  111. [132]D’Cruz PM Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat Human molecular genetics 9 645 651 2000 10699188
  112. [133]Lu Q Lemke G Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family Science 293 306 311 2001 11452127
  113. [134]Neher JJ Phagocytosis executes delayed neuronal death after focal brain ischemia Proceedings of the National Academy of Sciences of the United States of America 110 E4098 4107 2013 24101459 PMC3808587
  114. [135]Prasad D TAM receptor function in the retinal pigment epithelium Molecular and cellular neurosciences 33 96 108 2006 16901715
  115. [138]Acharya M alphav Integrin expression by DCs is required for Th17 cell differentiation and development of experimental autoimmune encephalomyelitis in mice The Journal of clinical investigation 120 4445 4452 2010 21099114 PMC2993596
  116. [139]Lacy-Hulbert A Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins Proceedings of the National Academy of Sciences of the United States of America 104 15823 15828 2007 17895374 PMC1994135
  117. [140]McCarty JH Selective ablation of alphav integrins in the central nervous system leads to cerebral hemorrhage, seizures, axonal degeneration and premature death Development 132 165 176 2005 15576410
  118. [141]McCarty JH Genetic ablation of alphav integrins in epithelial cells of the eyelid skin and conjunctiva leads to squamous cell carcinoma The American journal of pathology 172 1740 1747 2008 18467691 PMC2408432
  119. [142]Nandrot EF Finnemann SC Lack of alphavbeta5 integrin receptor or its ligand MFG-E8: distinct effects on retinal function Ophthalmic research 40 120 123 2008 18421224 PMC3237195
  120. [143]Aziz M Matsuda A Yang WL Jacob A Wang P Milk fat globule-epidermal growth factor-factor 8 attenuates neutrophil infiltration in acute lung injury via modulation of CXCR2 J Immunol 189 393 402 2012 22634615 PMC3382007
  121. [144]Fricker M MFG-E8 mediates primary phagocytosis of viable neurons during neuroinflammation The Journal of neuroscience: the official journal of the Society for Neuroscience 32 2657 2666 2012 22357850 PMC3312099
  122. [146]Kusunoki R Role of milk fat globule-epidermal growth factor 8 in colonic inflammation and carcinogenesis Journal of gastroenterology 2015 25596854
  123. [147]Neher JJ Neniskyte U Brown GC Primary phagocytosis of neurons by inflamed microglia: potential roles in neurodegeneration Frontiers in pharmacology 3 27 2012 22403545 PMC3288722
  124. [148]Peng Y Elkon KB Autoimmunity in MFG-E8-deficient mice is associated with altered trafficking and enhanced cross-presentation of apoptotic cell antigens The Journal of clinical investigation 121 2221 2241 2011 21537078 PMC3104739
  125. [150]Akitake-Kawano R Inhibitory role of Gas6 in intestinal tumorigenesis Carcinogenesis 34 1567 1574 2013 23430954
  126. [152]Binder MD Gas6 deficiency increases oligodendrocyte loss and microglial activation in response to cuprizone-induced demyelination The Journal of neuroscience: the official journal of the Society for Neuroscience 28 5195 5206 2008 18480276 PMC3844801
  127. [153]Binder MD Gas6 increases myelination by oligodendrocytes and its deficiency delays recovery following cuprizone-induced demyelination PloS one 6 e17727 2011 21423702 PMC3053381
  128. [154]Burnier L Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease Blood 115 3390 3397 2010 20139094 PMC2858482
  129. [155]Llacuna L Growth arrest-specific protein 6 is hepatoprotective against murine ischemia/reperfusion injury Hepatology 52 1371 1379 2010 20730776 PMC2947564
  130. [156]Yanagita M Essential role of Gas6 for glomerular injury in nephrotoxic nephritis The Journal of clinical investigation 110 239 246 2002 12122116 PMC151046
  131. [157]Cai L Wang Z Ji A Meyer JM van der Westhuyzen DR Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity PloS one 7 e36785 2012 22615812 PMC3353961
  132. [158]Greenberg ME Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells The Journal of experimental medicine 203 2613 2625 2006 17101731 PMC2118161
  133. [159]Kennedy DJ Dietary cholesterol plays a role in CD36-mediated atherogenesis in LDLR-knockout mice Arteriosclerosis, thrombosis, and vascular biology 29 1481 1487 2009 PMC2756023 19608973
  134. [160]Parks BW CD36, but not G2A, modulates efferocytosis, inflammation, and fibrosis following bleomycin-induced lung injury Journal of lipid research 54 1114 1123 2013 23393303 PMC3605987
  135. [161]Overton CD Yancey PG Major AS Linton MF Fazio S Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse Circulation research 100 670 677 2007 17303763
  136. [163]Yancey PG Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent Circulation 124 454 464 2011 21730304 PMC3144781
  137. [164]Subramanian M An AXL/LRP-1/RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo The Journal of clinical investigation 124 1296 1308 2014 24509082 PMC3934164
  138. [165]Ramirez-Ortiz ZG The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity Nature immunology 14 917 926 2013 23892722 PMC3752698
  139. [166]Bhatia VK Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor-deficient mice The American journal of pathology 170 416 426 2007 17200212 PMC1762701
  140. [167]Bossi F C1q as a unique player in angiogenesis with therapeutic implication in wound healing Proceedings of the National Academy of Sciences of the United States of America 111 4209 4214 2014 24591625 PMC3964125
  141. [168]Botto M Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies Nature genetics 19 56 59 1998 9590289
  142. [169]Chu Y Enhanced synaptic connectivity and epilepsy in C1q knockout mice Proceedings of the National Academy of Sciences of the United States of America 107 7975 7980 2010 20375278 PMC2867906
  143. [170]Stevens B The classical complement cascade mediates CNS synapse elimination Cell 131 1164 1178 2007 18083105

Cited by

Sorted by citations

Authors
Arandjelovic, S., & Ravichandran, K. S.
Affiliations
University of Virginia (US)
Corresponding author
Ravichandran, Kodi S
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2015-08-19
Volume
16
Issue
9
Pages
907-917
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.3253
PMC
PMC4826466
OpenAlex
W1832818975
Cited by
959
References
26
Citations by year
2026: 91 · 2025: 102 · 2024: 89 · 2023: 118 · 2022: 95 · 2021: 133 · 2020: 88 · 2019: 74 · 2018: 63 · 2017: 56 · 2016: 46 · 2015: 3 · 2013: 1
FWCI
5.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (NIGMS GM064709, GM064709, HL120840)
  • National Heart, Lung, and Blood Institute (HL120840, P01HL120840)
  • National Institute of Mental Health (R01MH096484, MH096484)
  • National Institute of General Medical Sciences (GM-064709, R01GM107848, R01GM064709, GM107848)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD074981, R01HD074981, R01HD057242)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
efferocytosis, phagocytosis, immune homeostasis, professional phagocytes, non-professional phagocytes, tissue homeostasis, cell turnover, programmed cell death
MeSH terms
Homeostasis, Humans, Phagocytes, Phagocytosis, Apoptosis

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 ›

Are you an author, or do you see a problem with this page? Request a review