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The scavenger receptor SCARF1 mediates apoptotic cell clearance and prevents autoimmunity

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2013

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Ramirez-Ortiz, Zaida G., William F. Pendergraft, Amit Prasad, Michael H. Byrne, Tal Iram, Christopher J. Blanchette, Andrew D. Luster, Nir Hacohen, Joseph El Khoury, and Terry K. Means. 2013. “The scavenger receptor SCARF1 mediates apoptotic cell clearance and prevents autoimmunity.” Nature immunology 14 (9): 917-926. doi:10.1038/ni.2670. http://dx.doi.org/10.1038/ni.2670.

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Clearance of apoptotic cells is critical for control of tissue homeostasis however the full range of receptor(s) on phagocytes responsible for recognition of apoptotic cells remains to be identified. Here we show that dendritic cells (DCs), macrophages and endothelial cells use scavenger receptor type F family member 1 (SCARF1) to recognize and engulf apoptotic cells via C1q. Loss of SCARF1 impairs uptake of apoptotic cells. Consequently, in SCARF1-deficient mice, dying cells accumulate in tissues leading to a lupus-like disease with the spontaneous generation of autoantibodies to DNA-containing antigens, immune cell activation, dermatitis and nephritis. The discovery of SCARF1 interactions with C1q and apoptotic cells provides insights into molecular mechanisms involved in maintenance of tolerance and prevention of autoimmune disease.

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