title: miR-22 controls Irf8 mRNA abundance and murine dendritic cell development.
abstract: MicroRNAs (miRNAs) have emerged as critical regulators of many cellular responses, through the action of miRNA-induced silencing complex (miRISC)- or miRNA ribonucleoprotein complex (miRNP)-mediated gene repression. Here we studied the role of miRNAs in the development of dendritic cells (DCs), an important immune cell type that is divided into conventional DC (cDC) and plasmacytoid DC (pDC) subsets. We found that miR-22 was highly expressed in mouse CD11c(+) CD11b(+) B220(-) cDCs compared to pDCs, and was induced in DC progenitor cell cultures with GM-CSF, which stimulate CD11c(+) CD11b(+) B220(-) cDC differentiation. Enforced overexpression of miR-22 during DC development enhanced CD11c(+) CD11b(+) B220(-) cDC generation at the expense of pDCs, while miR-22 knockdown demonstrated opposite effects. Moreover, overexpression and knockdown of miR-22 showed significant effects on the mRNA abundance of Irf8, which encodes the transcription factor IRF8 that plays essential roles in DC development. Luciferase reporter assays confirmed that miR-22 binds directly to the 3'UTR of the mouse Irf8 mRNA. Collectively, these results suggest that miR-22 targets Irf8 mRNA for posttranscriptional repression and controls DC subset differentiation.
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. haiyanli@mdanderson.org
authors.forename: Haiyan S
authors.initials: HS
authors.lastname: Li
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Greeley
authors.forename: Naoshi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Watowich
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
chemical_list: D020413:3' Untranslated Regions; D039481:CD11b Antigen; D039521:CD11c Antigen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D050835:Interferon Regulatory Factors; D017493:Leukocyte Common Antigens; D035683:MicroRNAs; D012333:RNA, Messenger; D000099185:Interferon Regulatory Factor-8; C574876:Mirn22 microRNA, mouse