PNAS：先天免疫中的lincRNA

　　

生物通报道：Sanford-Burnham医学研究所的科学家们发现，在病原体入侵使特定白细胞（巨噬细胞）激活时，生成了新的复合体。研究显示，这一复合体参与了免疫应答的调控，而且与川崎病（Kawasaki disease）有关。文章发表在美国科学院院刊PNAS杂志上。

巨噬细胞是免疫系统的第一道防线，它能发送信号（如TNF-alpha）为免疫系统敲响警钟。人们已经知道，在一些免疫相关的疾病中，TNF-alpha会促进炎症和组织破坏。一些抗TNF的药物，已被用来治疗类风湿关节炎和牛皮癣等炎症性疾病。

哺乳动物的基因组中，存在大量的基因间长链非编码RNA（lincRNA），这些lincRNA在多种生物学过程中起着重要的作用。研究人员利用芯片，鉴定了与先天免疫应答有关的lincRNA。他们发现，在免疫系统激活时，一个lincRNA与hnRNPL结合形成了功能性的复合体。

研究显示，上述复合体参与了对TNF-alpha的遗传学控制，而TNF-alpha是能促进炎症的强力细胞因子。研究人员将形成复合体的lincRNA命名为THRIL（TNF-alpha and hnRNPL-related immunoregulatory lincRNA）。文章指出，THRIL不仅与川崎病有关，可能还涉及了其它的炎症，例如类风湿关节炎和炎症性肠病等。

非编码RNA是免疫应答的关键调节子

“在机体对微生物病原体的免疫应答中，非编码RNA具有重要的作用，”文章的资深作者Tariq Rana教授说。

川崎病是一种罕见的儿童疾病，与血管发炎有关。有时这种疾病会影响冠状动脉，导致严重的心脏问题。所有种族、性别和年龄的儿童都可能受到川崎病的影响，不过这种疾病最常发生在亚洲和太平洋岛屿地区。

川崎病的典型症状包括眼睛、嘴唇、手掌和脚底发红，而这些都是血管发炎的标志。目前，人们还不知道这种疾病的病因，无法加以预防。尽管川崎病的治疗效果一般较好，但仍有少数患者可能死于川崎病引起的冠状动脉瘤。

研究团队在川崎病患者的样本中，检测不同疾病阶段的THRIL水平。他们发现，在疾病的急性期THRIL水平最低，而此时TNF-alpha的水平最高。研究指出，THRIL不仅可以作为免疫活化的新指标，还是治疗炎症性疾病的潜在靶点。

 

（生物通编辑：叶予）

生物通推荐原文摘要：

The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL

Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFα expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992–hnRNPL complex that regulated transcription of the TNFα gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNFα expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNFα and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNFα expression and may play important roles in the innate immune response and inflammatory diseases in humans.