Autoimmune Disease and Impaired Uptake of Apoptotic Cells in MFG-E8-Deficient Mice

阅读量:

185

作者:

R HanayamaM TanakaK MiyasakaK AozasaM KoikeY Uchiyama

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摘要:

Apoptotic cells expose phosphatidylserine and are swiftly engulfed by macrophages. Milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and that enhances the engulfment of apoptotic cells by macrophages. We report that tingible body macrophages in the germinal centers of the spleen and lymph nodes strongly express MFG-E8. Many apoptotic lymphocytes were found on the$MFG-E8^{-/-}$tingible body macrophages, but they were not efficiently engulfed. The$MFG-E8^{-/-}$mice developed splenomegaly, with the formation of numerous germinal centers, and suffered from glomerulonephritis as a result of autoantibody production. These data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in the germinal centers and that its failure can lead to autoimmune diseases.

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DOI:

10.1126/science.1094359

被引量:

1559

年份:

2004

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2012
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