MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure.
Apoptotic cells are swiftly engulfed by macrophages and immature dendritic cells. Inefficient clearance of apoptotic cells has been implicated as a cause of inflammation and autoimmune diseases. Milk fat globule-EGF factor 8 (MFG-E8) and developmental endothelial locus-1 (Del-1) are glycoproteins secreted from macrophages that pass apoptotic cells to phagocytes. MFG-E8, but not Del-1, is expressed in the tingible-body macrophages at the germinal centers of the second lymphoid tissues. MFG-E8-deficient mice carry many unengulfed apoptotic cells in the germinal centers of the spleen, and develop a lupus-like autoimmune disease. In this review, we discuss the importance of the MFG-E8-mediated clearance of apoptotic cells in the prevention of autoimmune diseases.
Hanayama
Rikinari
R
Department of Genetics, Osaka University Medical School, Osaka, Japan.
Miyasaka
Kay
K
Nakaya
Michio
M
Nagata
Shigekazu
S
D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000209:etiology*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology; D015815:Cell Adhesion Molecules; D003851:Deoxyribonucleases / Q000502:physiology; D018858:Germinal Center / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000502:physiology; D008894:Milk Proteins; D010587:Phagocytosis
D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; C098942:MFGE8 protein, human; D008894:Milk Proteins; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease