内源性双链 Alu RNA 元件在复发缓解型多发性硬化中刺激 IFN-反应。
Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis.
机构信息
Departments of Medicine, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Departments of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
出版信息
J Autoimmun. 2019 Jun;100:40-51. doi: 10.1016/j.jaut.2019.02.003. Epub 2019 Feb 28.
Various sensors that detect double-stranded RNA, presumably of viral origin, exist in eukaryotic cells and induce IFN-responses. Ongoing IFN-responses have also been documented in a variety of human autoimmune diseases including relapsing-remitting multiple sclerosis (RRMS) but their origins remain obscure. We find increased IFN-responses in leukocytes in relapsing-remitting multiple sclerosis at distinct stages of disease. Moreover, endogenous RNAs isolated from blood cells of these same patients recapitulate this IFN-response if transfected into naïve cells. These endogenous RNAs are double-stranded RNAs, contain Alu and Line elements and are transcribed from leukocyte transcriptional enhancers. Thus, transcribed endogenous retrotransposon elements can co-opt pattern recognition sensors to induce IFN-responses in RRMS.
各种检测双链 RNA 的传感器，推测来自病毒，存在于真核细胞中，并诱导 IFN 反应。持续的 IFN 反应也在多种人类自身免疫性疾病中得到证实，包括复发缓解型多发性硬化症（RRMS），但其起源仍不清楚。我们发现复发缓解型多发性硬化症患者在疾病的不同阶段白细胞中 IFN 反应增加。此外，如果将这些内源性 RNA 从同一患者的血细胞中分离出来并转染到未成熟细胞中，它们可以再现这种 IFN 反应。这些内源性 RNA 是双链 RNA，含有 Alu 和 Line 元件，由白细胞转录增强子转录。因此，转录的内源性逆转录转座子元件可以劫持模式识别传感器，在 RRMS 中诱导 IFN 反应。
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