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Autoimmune Disease and Impaired Uptake of Apoptotic Cells in MFG-E8-Deficient Mice
Abstract
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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“The best characterized of these are the soluble protein MFG-E8 87,121 and the glycolipid-anchored protein Tim-4 88.”
From Immunogenic and tolerogenic cell death (2009) · cites this paper as [88]
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Metadata
- Authors
- Hanayama, R., Tanaka, M., Miyasaka, K., Aozasa, K., Koike, M., Uchiyama, Y., & Nagata, S.
- Affiliations
- RIKEN (JP)
- Corresponding author
- Nagata, Shigekazu
- Venue
- Science
- Published
- 2004-05-21
- Volume
- 304
- Issue
- 5674
- Pages
- 1147-1150
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2037393136
- Cited by
- 992
- References
- 24
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 32 · 2023: 37 · 2022: 34 · 2021: 48 · 2020: 36 · 2019: 36 · 2018: 41 · 2017: 46 · 2016: 32 · 2015: 42 · 2014: 51 · 2013: 64 · 2012: 59
- FWCI
- 21.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- MFG-E8, efferocytosis, phosphatidylserine, macrophages, tingible body macrophages, germinal center, splenomegaly, glomerulonephritis, autoantibodies, autoimmune disease, B cell apoptosis
- MeSH terms
- CD68 Molecule, Animals, Antigens, Surface, Antibodies, Antinuclear, Autoantibodies, Autoimmune Diseases, B-Lymphocytes, Female, Glomerulonephritis, Macrophage Activation, Macrophages, Membrane Glycoproteins, Milk Proteins, Phagocytosis, Phosphatidylserines, Protein Binding, Spleen, Splenomegaly, T-Lymphocytes, Blotting, Northern, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Apoptosis, Macrophages, Peritoneal, Gene Targeting, Germinal Center, In Situ Nick-End Labeling, Mice
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