title: Transcriptomics identified a critical role for Th2 cell-intrinsic miR-155 in mediating allergy and antihelminth immunity.
abstract: Allergic diseases, orchestrated by hyperactive CD4(+) Th2 cells, are some of the most common global chronic diseases. Therapeutic intervention relies upon broad-scale corticosteroids with indiscriminate impact. To identify targets in pathogenic Th2 cells, we took a comprehensive approach to identify the microRNA (miRNA) and mRNA transcriptome of highly purified cytokine-expressing Th1, Th2, Th9, Th17, and Treg cells both generated in vitro and isolated ex vivo from allergy, infection, and autoimmune disease models. We report here that distinct regulatory miRNA networks operate to regulate Th2 cells in house dust mite-allergic or helminth-infected animals and in vitro Th2 cells, which are distinguishable from other T cells. We validated several miRNA (miR) candidates (miR-15a, miR-20b, miR-146a, miR-155, and miR-200c), which targeted a suite of dynamically regulated genes in Th2 cells. Through in-depth studies using miR-155(-/-) or miR-146a(-/-) T cells, we identified that T-cell-intrinsic miR-155 was required for type-2 immunity, in part through regulation of S1pr1, whereas T-cell-intrinsic miR-146a was required to prevent overt Th1/Th17 skewing. These data identify miR-155, but not miR-146a, as a potential therapeutic target to alleviate Th2-medited inflammation and allergy.
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Isobel S
authors.initials: IS
authors.lastname: Okoye
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Czieso
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Eleni
authors.initials: E
authors.lastname: Ktistaki
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Roderick
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Coomes
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Pelly
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Yashaswini
authors.initials: Y
authors.lastname: Kannan
authors.affiliation: Divisions of Molecular Immunology and.
authors.forename: Jimena
authors.initials: J
authors.lastname: Perez-Lloret
authors.affiliation: University of California, Los Angeles, CA 90095; andCalifornia Institute of Technology, Pasadena, CA 91125.
authors.forename: Jimmy L
authors.initials: JL
authors.lastname: Zhao
authors.affiliation: California Institute of Technology, Pasadena, CA 91125.
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
authors.affiliation: Parasitology, Medical Research Council, National Institute for Medical Research, London NW7 1AA, United Kingdom;
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
authors.affiliation: Divisions of Molecular Immunology and mwilson@nimr.mrc.ac.uk.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D006374:Helminthiasis, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000276:immunology; D000081025:Sphingosine-1-Phosphate Receptors; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C532623:Mirn155 microRNA, mouse; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors