title: The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity.
abstract: The clearance of apoptotic cells is critical for the control of tissue homeostasis; however, the full range of receptors on phagocytes responsible for the recognition of apoptotic cells remains to be identified. Here we found that dendritic cells (DCs), macrophages and endothelial cells used the scavenger receptor SCARF1 to recognize and engulf apoptotic cells via the complement component C1q. Loss of SCARF1 impaired the uptake of apoptotic cells. Consequently, in SCARF1-deficient mice, dying cells accumulated in tissues, which led to a lupus-like disease, with the spontaneous generation of autoantibodies to DNA-containing antigens, activation of cells of the immune system, dermatitis and nephritis. The discovery of such interactions of SCARF1 with C1q and apoptotic cells provides insight into the molecular mechanisms involved in the maintenance of tolerance and prevention of autoimmune disease.
authors.affiliation: Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Zaida G
authors.initials: ZG
authors.lastname: Ramirez-Ortiz
authors.forename: William F
authors.initials: WF
authors.lastname: Pendergraft
authors.forename: Amit
authors.initials: A
authors.lastname: Prasad
authors.forename: Michael H
authors.initials: MH
authors.lastname: Byrne
authors.forename: Tal
authors.initials: T
authors.lastname: Iram
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Blanchette
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Nir
authors.initials: N
authors.lastname: Hacohen
authors.forename: Joseph
authors.initials: J
authors.lastname: El Khoury
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D015922:Complement C1q / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009393:Nephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D011485:Protein Binding; D051128:Scavenger Receptors, Class F / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D051128:Scavenger Receptors, Class F; D012694:Serine; D015922:Complement C1q
references.citation: Nature. 2002 May 9;417(6885):182-7
references.pmid: 12000961
references.citation: Science. 2004 May 21;304(5674):1147-50
references.pmid: 15155946
references.citation: Cell Host Microbe. 2007 Dec 13;2(6):393-403
references.pmid: 18078691
references.citation: Bioorg Med Chem. 2002 Aug;10(8):2445-60
references.pmid: 12057634
references.citation: Nat Neurosci. 2009 Dec;12(12):1534-41
references.pmid: 19915564
references.citation: Immunity. 2007 Dec;27(6):927-40
references.pmid: 18082433
references.citation: Mol Cell. 2004 May 7;14(3):277-87
references.pmid: 15125832
references.citation: J Exp Med. 1994 Apr 1;179(4):1317-30
references.pmid: 7511686
references.citation: Immunity. 2005 May;22(5):551-60
references.pmid: 15894273
references.citation: PLoS One. 2006 Dec 27;1:e120
references.pmid: 17205124
references.citation: Cell Death Differ. 2008 Feb;15(2):243-50
references.pmid: 17571081
references.citation: Lupus. 2008 May;17(5):371-5
references.pmid: 18490410
references.citation: N Engl J Med. 2011 Dec 1;365(22):2110-21
references.pmid: 22129255
references.citation: J Leukoc Biol. 2012 Sep;92(3):489-97
references.pmid: 22715140
references.citation: J Biol Chem. 1997 Dec 12;272(50):31217-20
references.pmid: 9395444
references.citation: J Mol Biol. 2011 Apr 29;408(2):277-90
references.pmid: 21352829
references.citation: J Neurosci. 2012 Sep 19;32(38):13022-31
references.pmid: 22993420
references.citation: J Biol Chem. 2004 Dec 3;279(49):51250-7
references.pmid: 15371419
references.citation: Virulence. 2010 Jan-Feb;1(1):37-41
references.pmid: 21178411
references.citation: J Biol Chem. 2002 Apr 5;277(14):11772-9
references.pmid: 11729193
references.citation: Nat Genet. 1998 May;19(1):56-9
references.pmid: 9590289
references.citation: J Cell Biol. 2010 Jun 28;189(7):1059-70
references.pmid: 20584912
references.citation: Adv Exp Med Biol. 2009;653:1-14
references.pmid: 19799108
references.citation: J Exp Med. 2000 Aug 7;192(3):359-66
references.pmid: 10934224
references.citation: Nature. 2001 Jul 12;412(6843):198-202
references.pmid: 11449278
references.citation: J Immunol. 2008 Feb 15;180(4):2329-38
references.pmid: 18250442
references.citation: J Leukoc Biol. 2011 Sep;90(3):447-57
references.pmid: 21562053
references.citation: Annu Rev Immunol. 2004;22:431-56
references.pmid: 15032584
references.citation: J Biol Chem. 2004 Jul 23;279(30):30938-44
references.pmid: 15145948
references.citation: Cell. 2010 Mar 5;140(5):619-30
references.pmid: 20211132
references.citation: J Immunol. 1992 Apr 1;148(7):2207-16
references.pmid: 1545126
references.citation: J Exp Med. 2009 Mar 16;206(3):637-53
references.pmid: 19237602
references.citation: Arthritis Res Ther. 2011 Feb 28;13(1):202
references.pmid: 21371352
references.citation: J Clin Invest. 1977 Jan;59(1):90-6
references.pmid: 299748
references.citation: Arthritis Rheum. 1982 Nov;25(11):1271-7
references.pmid: 7138600
references.citation: Nature. 2007 Nov 15;450(7168):430-4
references.pmid: 17960134
references.citation: Nat Rev Immunol. 2007 Dec;7(12):964-74
references.pmid: 18037898
references.citation: J Exp Med. 2001 Sep 17;194(6):781-95
references.pmid: 11560994
references.citation: Cell. 2005 Oct 21;123(2):321-34
references.pmid: 16239148
references.citation: Int Immunol. 2012 Sep;24(9):551-9
references.pmid: 22723547
references.citation: J Immunol. 2012 Apr 15;188(8):4113-21
references.pmid: 22422888
references.citation: Cell Immunol. 2011;267(2):88-93
references.pmid: 21190681
references.citation: Autoimmun Rev. 2007 Jun;6(6):366-72
references.pmid: 17537382
references.citation: Cell. 2001 Jan 12;104(1):43-56
references.pmid: 11163239
references.citation: J Exp Med. 2002 May 20;195(10):1289-302
references.pmid: 12021309
references.citation: J Exp Med. 2002 Jul 1;196(1):135-40
references.pmid: 12093878
references.citation: Neuron. 2006 Jun 15;50(6):855-67
references.pmid: 16772168
references.citation: J Biol Chem. 2002 Oct 18;277(42):39696-702
references.pmid: 12154095
references.citation: J Immunol. 2010 Sep 1;185(5):2903-17
references.pmid: 20686127
references.citation: Proc Natl Acad Sci U S A. 2010 May 11;107(19):8712-7
references.pmid: 20421466