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- Title
The microRNA miR-155 controls CD8<sup>+</sup> T cell responses by regulating interferon signaling.
- Authors
Gracias, Donald T; Stelekati, Erietta; Hope, Jennifer L; Boesteanu, Alina C; Doering, Travis A; Norton, Jillian; Mueller, Yvonne M; Fraietta, Joseph A; Wherry, E John; Turner, Martin; Katsikis, Peter D
- 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.
- Subjects
MICRORNA; INTERFERONS; CELLULAR signal transduction; T cells; CD8 antigen; GENE expression
- Publication
Nature Immunology, 2013, Vol 14, Issue 6, p593
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2576