MicroRNA-directed program of cytotoxic CD8 + T-cell differentiation
| Autor: | Sara Trifari, Runqiang Chen, Gustavo J. Martinez, Anjana Rao, Matthew E. Pipkin, Jed A. Bassein, Hozefa S. Bandukwala, Tarmo Äijö |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Ribonuclease III
ta222 Cellular differentiation Blotting Western Eomesodermin chemical and pharmacologic phenomena Real-Time Polymerase Chain Reaction Granzymes CD8T-cell response Mice Animals Humans Cytotoxic T cell DNA Primers ta113 Multidisciplinary biology Perforin Effector Interleukin-2 Receptor alpha Subunit Computational Biology Cell Differentiation hemic and immune systems Sequence Analysis DNA Biological Sciences Adoptive Transfer Cell biology MicroRNAs CTL Gene Expression Regulation Granzyme Virus Diseases Immunology biology.protein Posttranscriptional regulation Signal Transduction T-Lymphocytes Cytotoxic Dicer |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:18608-18613 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1317191110 |
| Popis: | Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTLs, and that deletion or depletion of Dicer in mouse or human activated CD8(+) T cells causes up-regulation of perforin, granzymes, and effector cytokines. Genome-wide analysis of microRNA (miR, miRNA) changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of an miRNA network that controls perforin, eomesodermin, and IL-2Rα expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation, and antigenic stimulation. Overall, our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|