IL-4 Inhibits the Biogenesis of an Epigenetically Suppressive PIWI-Interacting RNA To Upregulate CD1a Molecules on Monocytes/Dendritic Cells

• Published in: The Journal of immunology (1950) 2016-02, Vol.196 (4), p.1591-1603
• Main Authors: Zhang, Xue, He, Xin, Liu, Chao, Liu, Jun, Hu, Qifei, Pan, Ting, Duan, Xiaobing, Liu, Bingfeng, Zhang, Yiwen, Chen, Jingliang, Ma, Xingru, Zhang, Xu, Luo, Haihua, Zhang, Hui
• Format: Article
• Language: English
• Subjects: Antigens, CD1 - genetics; Antigens, CD1 - immunology; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - metabolism; Epigenomics; HEK293 Cells; Heterochromatin - metabolism; Humans; Interleukin-4 - metabolism; Monocytes - immunology; Promoter Regions, Genetic; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Sequence Analysis, DNA; Signal Transduction; Transcriptional Activation; Up-Regulation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500805

The discovery of PIWI-interacting RNAs (piRNAs) revealed the complexity of the RNA world. Although piRNAs were first deemed to be germline specific, substantial evidence shows their various roles in somatic cells; however, their function in highly differentiated immune cells remains elusive. In this study, by initially screening with a small RNA deep-sequencing analysis, we found that a piRNA, tRNA-Glu-derived piRNA [td-piR(Glu)], was expressed much more abundantly in human monocytes than in dendritic cells. By regulating the polymerase III activity, IL-4 potently decreased the biogenesis of tRNA-Glu and, subsequently, td-piR(Glu). Further, we revealed that the td-piR(Glu)/PIWIL4 complex recruited SETDB1, SUV39H1, and heterochromatin protein 1β to the CD1A promoter region and facilitated H3K9 methylation. As a result, the transcription of CD1A was significantly inhibited. Collectively, we demonstrated that a piRNA acted as the signal molecule for a cytokine to regulate the expression of an important membrane protein for lipid Ag presentation.