title: MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells.
abstract: MicroRNA (miRNA)-deficient helper T cells exhibit abnormal IFN-γ production and decreased proliferation. However, the contributions of individual miRNAs to this phenotype remain poorly understood. We conducted a screen for miRNA function in primary T cells and identified individual miRNAs that rescue the defects associated with miRNA deficiency. Multiple members of the miR-17 and miR-92 families enhanced miRNA-deficient T cell proliferation whereas miR-29 largely corrected their aberrant interferon-γ (IFN-γ) expression. Repression of IFN-γ production by miR-29 involved direct targeting of both T-bet and Eomes, two transcription factors known to induce IFN-γ production. Although not usually expressed at functionally relevant amounts in helper T cells, Eomes was abundant in miRNA-deficient cells and was upregulated after miR-29 inhibition in wild-type cells. These results demonstrate that miR-29 regulates helper T cell differentiation by repressing multiple target genes, including at least two that are independently capable of inducing the T helper 1 (Th1) cell gene expression program.
authors.affiliation: Sandler Asthma Basic Research Center and Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Steiner
authors.forename: Molly F
authors.initials: MF
authors.lastname: Thomas
authors.forename: Joyce K
authors.initials: JK
authors.lastname: Hu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Babiarz
authors.forename: Christopher D C
authors.initials: CD
authors.lastname: Allen
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Matloubian
authors.forename: Robert
authors.initials: R
authors.lastname: Blelloch
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D020825:T-Box Domain Proteins / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D016207:Cytokines; C474044:Dgcr8 protein, mouse; C491198:Eomes protein, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D011506:Proteins; D016601:RNA-Binding Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma