title: IL-23 receptor regulation by Let-7f in human CD4+ memory T cells.
abstract: CD4(+) memory T cells include the Th17 cell population, which has been shown to be implicated in autoimmune and inflammatory diseases. These memory T cells express higher IL-23R and produce more IL-17 compared with their naive counterparts. However, the molecular mechanisms that regulate IL-23R expression in human T cells are not completely understood. MicroRNAs play important roles in a wide range of biological events through posttranscriptional suppression of target mRNAs. In this article, we provide evidence that a specific microRNA, Let-7f, inhibits IL-23R expression in human CD4(+) memory T cells. Endogenous expression of Let-7f in memory T cells is significantly lower when compared with naive T cells, and Let-7f blocks IL-23R expression through its complementary target sequence within 3' untranslated region of target gene. Furthermore, exogenous transfection of a Let-7f mimic into memory T cells results in downregulation of IL-23R and its downstream cytokine, IL-17. Our findings reveal a novel mechanism in regulating the IL-23/IL-23R pathway and subsequent downstream IL-17 production, which may provide novel therapeutics for human inflammatory and autoimmune diseases.
authors.affiliation: Division of Gastroenterology, Department of Medicine, School of Medicine, Harvey M and Lyn P Meyerhoff Inflammatory Bowel Disease Center, The Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Steven R
authors.initials: SR
authors.lastname: Brant
authors.forename: John H
authors.initials: JH
authors.lastname: Kwon
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics* / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; C515500:IL23R protein, human; D020381:Interleukin-17; D035683:MicroRNAs; D012333:RNA, Messenger; D018123:Receptors, Interleukin; C487931:mirnlet7 microRNA, human; D008156:Luciferases; D017493:Leukocyte Common Antigens