生物通報道：Sanford-Burnham醫(yī)學研究所的科學家們發(fā)現(xiàn)，在病原體入侵使特定白細胞（巨噬細胞）激活時，生成了新的復合體。研究顯示，這一復合體參與了免疫應答的調控，而且與川崎�。�Kawasaki disease）有關。文章發(fā)表在美國科學院院刊PNAS雜志上。

巨噬細胞是免疫系統(tǒng)的第一道防線，它能發(fā)送信號（如TNF-alpha）為免疫系統(tǒng)敲響警鐘。人們已經(jīng)知道，在一些免疫相關的疾病中，TNF-alpha會促進炎癥和組織破壞。一些抗TNF的藥物，已被用來治療類風濕關節(jié)炎和牛皮癬等炎癥性疾病。

哺乳動物的基因組中，存在大量的基因間長鏈非編碼RNA（lincRNA），這些lincRNA在多種生物學過程中起著重要的作用。研究人員利用芯片，鑒定了與先天免疫應答有關的lincRNA。他們發(fā)現(xiàn)，在免疫系統(tǒng)激活時，一個lincRNA與hnRNPL結合形成了功能性的復合體。

研究顯示，上述復合體參與了對TNF-alpha的遺傳學控制，而TNF-alpha是能促進炎癥的強力細胞因子。研究人員將形成復合體的lincRNA命名為THRIL（TNF-alpha and hnRNPL-related immunoregulatory lincRNA）。文章指出，THRIL不僅與川崎病有關，可能還涉及了其它的炎癥，例如類風濕關節(jié)炎和炎癥性腸病等。

非編碼RNA是免疫應答的關鍵調節(jié)子

“在機體對微生物病原體的免疫應答中，非編碼RNA具有重要的作用，”文章的資深作者Tariq Rana教授說。

川崎病是一種罕見的兒童疾病，與血管發(fā)炎有關。有時這種疾病會影響冠狀動脈，導致嚴重的心臟問題。所有種族、性別和年齡的兒童都可能受到川崎病的影響，不過這種疾病最常發(fā)生在亞洲和太平洋島嶼地區(qū)。

川崎病的典型癥狀包括眼睛、嘴唇、手掌和腳底發(fā)紅，而這些都是血管發(fā)炎的標志。目前，人們還不知道這種疾病的病因，無法加以預防。盡管川崎病的治療效果一般較好，但仍有少數(shù)患者可能死于川崎病引起的冠狀動脈瘤。

研究團隊在川崎病患者的樣本中，檢測不同疾病階段的THRIL水平。他們發(fā)現(xiàn)，在疾病的急性期THRIL水平最低，而此時TNF-alpha的水平最高。研究指出，THRIL不僅可以作為免疫活化的新指標，還是治療炎癥性疾病的潛在靶點。

（生物通編輯：葉予）

生物通推薦原文摘要：

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.