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The microRNA miR-155 controls CD8+ T cell responses by regulating interferon signaling

2013; Nature Portfolio; Volume: 14; Issue: 6 Linguagem: Inglês

10.1038/ni.2576

1529-2916

Donald T. Gracias, Erietta Stelekati, Jennifer L. Hope, Alina C. Boesteanu, Travis A. Doering, Jillian Norton, Yvonne M. Mueller, Joseph A. Fraietta, E. John Wherry, Martin Turner, Peter D. Katsikis,

Cancer-related molecular mechanisms research

The roles of individual microRNAs in the CD8+ T cell response remain mostly unexplored. Katsikis and colleagues show that miR-155 regulates type I interferon responsiveness and CD8+ T cell responses to pathogens in vivo. 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.