title: A Novel miR-24-TCF1 Axis in Modulating Effector T Cell Responses.
abstract: miR-23∼27∼24 was recently implicated in restricting Th2 immunity, as well as the differentiation and function of other effector T cell lineages. Interestingly, miR-24, unlike other family members, actually promotes Th1 and Th17 responses. In this article, we show that miR-24 drives the production of IFN-γ and IL-17 in T cells at least in part through targeting TCF1, a transcription factor known for its role in limiting Th1 and Th17 immunity. Surprisingly, whereas TCF1 was previously shown to promote Th2 responses through inducing GATA3, enforced TCF1 expression in miR-24-overexpressing T cells led to further downregulation of IL-4 and GATA3 expression, suggesting miR-24-mediated inhibition of Th2 immunity cannot be attributed to TCF1 repression by miR-24. Together, our data demonstrate a novel miR-24-TCF1 pathway in controlling effector cytokine production by T cells and further suggest miR-24 could function as a key upstream molecule regulating TCF1-mediated immune responses.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Sunglim
authors.initials: S
authors.lastname: Cho
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Cheng-Jang
authors.identifier: 0000-0002-7640-5915
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Duc T
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Lin
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Mei-Chi
authors.identifier: 0000-0002-9984-3459
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Toyota Technological Institute at Chicago, Chicago, IL 60637.
authors.forename: Aly Azeem
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Bi-Huei
authors.identifier: 0000-0003-3363-4408
authors.initials: BH
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Wenxian
authors.identifier: 0000-0003-0684-8929
authors.initials: W
authors.lastname: Fu
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093; lifanlu@ucsd.edu.|Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093; and.|Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Li-Fan
authors.identifier: 0000-0002-9727-0036
authors.initials: LF
authors.lastname: Lu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015536:Down-Regulation; D050990:GATA3 Transcription Factor / Q000096:biosynthesis; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D020381:Interleukin-17; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; D015847:Interleukin-4; D007371:Interferon-gamma