title: The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.
abstract: We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory CD8(+) T cells, but low miR-155 expression in naive and central memory cells. Antiviral CD8(+) T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to CD8(+) T cells, as miR-155-deficient CD8(+) T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral CD8(+) T cell responses in vivo. Gene-expression profiling showed that miR-155-deficient CD8(+) T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon-associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient CD8(+) T cells in vivo. We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and CD8(+) T cell responses to pathogens in vivo.
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology and Vaccine Science, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Donald T
authors.initials: DT
authors.lastname: Gracias
authors.forename: Erietta
authors.initials: E
authors.lastname: Stelekati
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hope
authors.forename: Alina C
authors.initials: AC
authors.lastname: Boesteanu
authors.forename: Travis A
authors.initials: TA
authors.lastname: Doering
authors.forename: Jillian
authors.initials: J
authors.lastname: Norton
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Mueller
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Fraietta
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.forename: Peter D
authors.initials: PD
authors.lastname: Katsikis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics / Q000276:immunology; D015151:Immunoblotting; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D050794:STAT1 Transcription Factor; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007372:Interferons