Zhang Nan-Nan, Shen Shu-Hong, Jiang Lin-Jia, Zhang Wu, Zhang Hong-Xin, Sun Yue-Ping, Li Xian-Yang, Huang Qiu-Hua, Ge Bao-Xue, Chen Sai-Juan, Wang Zhu-Gang, Chen Zhu, Zhu Jiang
State Key Laboratory for Medical Genomics, Institute of Health Science, Shanghai Institute for Biological Sciences and Graduate School, Chinese Academy of Sciences, People's Republic of China.
Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10553-8. doi: 10.1073/pnas.0804895105. Epub 2008 Jul 23.
RIG-I has been implicated in innate immunity by sensing intracellular viral RNAs and inducing type I IFN production. However, we have found a significant RIG-I induction in a biological setting without active viral infection-namely, during RA-induced terminal granulocytic differentiation of acute myeloid leukemias. Here, we present evidence that a significant Rig-I induction also occurs during normal myelopoiesis and that the disruption of the Rig-I gene in mice leads to the development of a progressive myeloproliferative disorder. The initiation of progressive myeloproliferative disorder is mainly due to an intrinsic defect of Rig-I(-/-) myeloid cells, which are characterized by a reduced expression of IFN consensus sequence binding protein, a major regulator of myeloid differentiation. Thus, our study reveals a critical regulatory role of Rig-I in modulating the generation and differentiation of granulocytes.
维甲酸诱导基因I（RIG-I）通过感知细胞内病毒RNA并诱导I型干扰素产生，参与固有免疫。然而，我们发现在无活性病毒感染的生物学环境中，即急性髓系白血病的维甲酸诱导终末粒细胞分化过程中，RIG-I有显著诱导。在此，我们提供证据表明，在正常骨髓生成过程中也会发生显著的RIG-I诱导，并且小鼠中RIG-I基因的破坏会导致进行性骨髓增殖性疾病的发展。进行性骨髓增殖性疾病的起始主要归因于RIG-I（-/-）髓系细胞的内在缺陷，其特征是干扰素共有序列结合蛋白（髓系分化的主要调节因子）表达降低。因此，我们的研究揭示了RIG-I在调节粒细胞生成和分化中的关键调节作用。
