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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.

SUBMITTER: Ramirez-Ortiz ZG

PROVIDER: S-EPMC3752698 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity.

Ramirez-Ortiz Zaida G ZG Pendergraft William F WF Prasad Amit A Byrne Michael H MH Iram Tal T Blanchette Christopher J CJ Luster Andrew D AD Hacohen Nir N El Khoury Joseph J Means Terry K TK

Nature immunology 20130728 9

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 ce ...[more]

PMID: 23892722

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Project description:IntroductionInadequate clearance of apoptotic cells by macrophages is one of the reasons for the breakdown of self-tolerance. Class A scavenger receptors, macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A), which are expressed on macrophages, play important roles in the uptake of apoptotic cells. A previous study reported the presence of the anti-MARCO antibody in lupus-prone mice and systemic lupus erythematosus (SLE) patients. The purpose of this study was to investigate the prevalence of anti-class A scavenger receptor antibodies in patients with various autoimmune diseases, in particular SLE, and the functional implication of those autoantibodies in the phagocytic clearance of apoptotic cells by macrophages.MethodsPurified recombinant scavenger receptor cysteine-rich (SRCR) polypeptide (ligand-binding domain of MARCO) and recombinant SR-A were used as antigens. By using enzyme-linked immunosorbent assay, the anti-SRCR and anti-SR-A antibodies were detected in the sera of untreated patients with SLE (n = 65), rheumatoid arthritis (n = 65), primary Sjögren syndrome (n = 25), and healthy blood donors (n = 85). The effect of IgG purified from SLE patients or healthy controls on the phagocytosis of apoptotic cells by macrophages was measured by the flow cytometry assay.ResultsAnti-SRCR antibodies were present in patients with SLE (18.5%) and rheumatoid arthritis (3.1%), but not in those with primary Sjögren syndrome. Anti-SR-A antibodies were present in patients with SLE (33.8%), rheumatoid arthritis (13.8%), and primary Sjögren syndrome (12.0%). IgG from SLE patients positive for anti-SRCR or anti-SR-A antibodies showed a higher inhibition rate on binding of apoptotic cells to macrophages than IgG from healthy controls (both P < 0.05). IgG from SLE patients positive for both anti-SRCR and anti-SR-A antibodies showed a significantly higher inhibition rate on ingestion of apoptotic by macrophages than IgG from healthy controls (P < 0.05).ConclusionsOur results indicated that autoantibodies to class A scavenger receptors might contribute to the breakdown of self-tolerance by impairing the clearance of apoptotic debris and play a role in the pathogenesis of autoimmune disease, especially in SLE.

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The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity.

Publications

The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity.

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