The innate immune system in host mice targets cells with allogenic mitochondrial DNA.
The innate immune system in host mice targets cells with allogenic mitochondrial DNA.
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DOI：
10.1084/jem.20092296
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发表时间：
2010-10-25
期刊：
影响因子：
--
通讯作者：
Hayashi J
中科院分区：
文献类型：
--
作者：
Ishikawa K;Toyama-Sorimachi N;Nakada K;Morimoto M;Imanishi H;Yoshizaki M;Sasawatari S;Niikura M;Takenaga K;Yonekawa H;Hayashi J
携带外源线粒体 DNA 的肿瘤或胚胎干细胞会通过依赖 MyD88 的机制被先天免疫系统排斥。线粒体DNA（mtDNA）被认为与呼吸功能有关，并且mtDNA突变与衰老、肿瘤和各种疾病有关，但mtDNA从不同个体或老年受试者输入移植物中的影响尚不清楚。我们通过生成跨线粒体肿瘤细胞和胚胎干细胞来研究这个问题，它们共享同源 C57BL/6 (B6) 品系来源的核 DNA 背景，但拥有来自同种异体小鼠品系的 mtDNA。我们证明，来自 NZB/B1NJ 品系的 mtDNA 移植物被宿主 B6 小鼠排斥，不是被后天免疫系统排斥，而是被先天免疫系统排斥。这种排斥反应部分是由 NK 细胞引起的，涉及 MyD88 依赖性途径。这些结果介绍了 mtDNA 和先天免疫在肿瘤免疫学和移植医学中的新作用。
Tumors or embryonic stem cells bearing foreign mitochondrial DNA are rejected by the innate immune system via a mechanism that depends on MyD88. Mitochondrial DNA (mtDNA) has been proposed to be involved in respiratory function, and mtDNA mutations have been associated with aging, tumors, and various disorders, but the effects of mtDNA imported into transplants from different individuals or aged subjects have been unclear. We examined this issue by generating trans-mitochondrial tumor cells and embryonic stem cells that shared the syngenic C57BL/6 (B6) strain–derived nuclear DNA background but possessed mtDNA derived from allogenic mouse strains. We demonstrate that transplants with mtDNA from the NZB/B1NJ strain were rejected from the host B6 mice, not by the acquired immune system but by the innate immune system. This rejection was caused partly by NK cells and involved a MyD88-dependent pathway. These results introduce novel roles of mtDNA and innate immunity in tumor immunology and transplantation medicine.
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