Mitochondrial transcription factor A serves as a danger signal by augmenting plasmacytoid dendritic cell responses to DNA.
Mitochondrial transcription factor A serves as a danger signal by augmenting plasmacytoid dendritic cell responses to DNA.
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DOI：
10.4049/jimmunol.1101375
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发表时间：
2012-07-01
期刊：
影响因子：
--
通讯作者：
Crouser ED
中科院分区：
文献类型：
--
作者：
Julian MW;Shao G;Bao S;Knoell DL;Papenfuss TL;VanGundy ZC;Crouser ED
浆细胞样树突状细胞（pDC）是一种有效的抗原呈递细胞，已知可调节对自身抗原，特别是DNA的免疫反应。坏死细胞的线粒体部分被发现最有效地促进了人类pDC的激活，这反映在I型干扰素的释放上，这依赖于线粒体DNA的存在，并涉及TLR9和晚期糖基化终产物（RAGE）的受体。线粒体转录因子A （TFAM）是一种在功能和结构上与高迁移率组盒蛋白1 （HMGB1）同源的高丰度线粒体蛋白，可与CpGA DNA协同促进人pDC活化。pDC I型干扰素对TFAM和CpGA DNA的应答表明它们分别与RAGE和TLR9有关，并依赖于内体加工和PI3K、ERK和NF-κB信号传导。总之，这些结果表明，pDC通过识别坏死细胞的线粒体成分来促进无菌免疫反应，并进一步证明TFAM和线粒体DNA可能是在这种情况下pDC激活的介质。
Plasmacytoid dendritic cells (pDC) are potent antigen-presenting cells known to regulate immune responses to self-antigens, particularly DNA. The mitochondrial fraction of necrotic cells was found to most potently promote human pDC activation, as reflected by Type I interferon release, which was dependent upon the presence of mitochondrial DNA and involved TLR9 and receptors for advanced glycation endproducts (RAGE). Mitochondrial transcription factor A (TFAM), a highly abundant mitochondrial protein that is functionally and structurally homologous to high-mobility group box protein 1 (HMGB1), was observed to synergize with CpGA DNA to promote human pDC activation. pDC Type I interferon responses to TFAM and CpGA DNA indicated their engagement with RAGE and TLR9, respectively, and were dependent upon endosomal processing and PI3K, ERK and NF-κB signaling. Together, these results indicate that pDC contribute to sterile immune responses by recognizing the mitochondrial component of necrotic cells and further incriminate TFAM and mitochondrial DNA as likely mediators of pDC activation under these circumstances.
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影响因子：
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DOI：
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发表时间：
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影响因子：
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作者：
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