Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice
Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice
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DOI：
10.1126/science.1094359
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发表时间：
2004-05-21
期刊：
影响因子：
56.9
通讯作者：
Nagata, S
中科院分区：
文献类型：
--
作者：
Hanayama, R;Tanaka, M;Nagata, S
凋亡细胞会暴露磷脂酰丝氨酸，并迅速被巨噬细胞吞噬。乳脂肪球表皮生长因子8（MFG - E8）是一种通过识别磷脂酰丝氨酸与凋亡细胞结合的蛋白质，它能增强巨噬细胞对凋亡细胞的吞噬作用。我们报道，在脾脏和淋巴结的生发中心，易染体巨噬细胞强烈表达MFG - E8。在MFG - E8基因敲除的易染体巨噬细胞上发现了许多凋亡的淋巴细胞，但它们没有被有效吞噬。MFG - E8基因敲除的小鼠出现脾肿大，伴有大量生发中心形成，并因自身抗体产生而患肾小球肾炎。这些数据表明，MFG - E8在清除生发中心的凋亡B细胞方面起着关键作用，其功能缺失可导致自身免疫性疾病。
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.