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

• Published in: Nature immunology Vol. 14; no. 9; pp. 917 - 926
• Main Authors: Ramirez-Ortiz, Zaida G, Pendergraft, 3rd, William F, Prasad, Amit, Byrne, Michael H, Iram, Tal, Blanchette, Christopher J, Luster, Andrew D, Hacohen, Nir, El Khoury, Joseph, Means, Terry K
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2013
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Apoptosis - immunology; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmunity; Autoimmunity - genetics; Complement C1q - chemistry; Complement C1q - immunology; Complement C1q - metabolism; Deoxyribonucleic acid; Dermatitis; DNA; Female; Genetic aspects; Immune system; Inflammation - genetics; Inflammation - immunology; Inflammation - metabolism; Male; Membrane proteins; Mice; Mice, Knockout; Nephritis - genetics; Nephritis - immunology; Nephritis - pathology; Phagocytosis - genetics; Phagocytosis - immunology; Phosphorylation; Physiological aspects; Prevention; Protein Binding; Scavenger Receptors, Class F - genetics; Scavenger Receptors, Class F - immunology; Scavenger Receptors, Class F - metabolism; Serine - metabolism; United States
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.2670

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.