Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation
Impaired thymic development in mouse embryos deficient in apoptotic DNA degradation
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DOI：
10.1038/ni881
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发表时间：
2003-02-01
影响因子：
30.5
通讯作者：
Nagata, S
中科院分区：
文献类型：
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作者：
Kawane, K;Fukuyama, H;Nagata, S
细胞凋亡通常伴随着染色体DNA的降解。Caspase-activated DNase （CAD）是一种在垂死细胞中被激活的内切酶，而DNase II则存在于巨噬细胞的溶酶体中。在这里，我们发现CAD（-/-）胸腺细胞没有发生凋亡性DNA降解。但是，当凋亡细胞被巨噬细胞吞噬时，它们的DNA被DNA酶II降解。DNA酶II-/- CAD（-/-）胚胎胸腺含有许多携带未消化DNA的灶，由于T细胞发育受阻，细胞结构严重降低。在DNase II-/- CAD（-/-）胚胎胸腺中，干扰素- β基因强烈上调，提示凋亡细胞的DNA未被消化时，可激活先天免疫，导致胸腺发育缺陷。
Apoptosis is often accompanied by the degradation of chromosomal DNA. Caspase-activated DNase (CAD) is an endonuclease that is activated in dying cells, whereas DNase II is present in the lysosomes of macrophages. Here, we show that CAD(-/-) thymocytes did not undergo apoptotic DNA degradation. But, when apoptotic cells were phagocytosed by macrophages, their DNA was degraded by DNase II. The thymus of DNase II-/- CAD(-/-) embryos contained many foci carrying undigested DNA and the cellularity was severely reduced due to a block in T cell development. The interferon-beta gene was strongly up-regulated in the thymus of DNase II-/- CAD(-/-) embryos, suggesting that when the DNA of apoptotic cells is left undigested, it can activate innate immunity leading to defects in thymic development.