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

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  • Rikinari Hanayama
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Masato Tanaka
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Kay Miyasaka
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Katsuyuki Aozasa
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Masato Koike
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Yasuo Uchiyama
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
  • Shigekazu Nagata
    Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.

書誌事項

公開日
2004-05-21
DOI
  • 10.1126/science.1094359
公開者
American Association for the Advancement of Science (AAAS)

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<jats:p> 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 <jats:italic>MFG-E8</jats:italic> <jats:sup>–/–</jats:sup> tingible body macrophages, but they were not efficiently engulfed. The <jats:italic>MFG-E8</jats:italic> <jats:sup>–/–</jats:sup> 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. </jats:p>

収録刊行物

  • Science

    Science 304 (5674), 1147-1150, 2004-05-21

    American Association for the Advancement of Science (AAAS)

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