| First Author | Amado T | Year | 2020 |
| Journal | J Mol Med (Berl) | Volume | 98 |
| Issue | 2 | Pages | 309-320 |
| PubMed ID | 32002568 | Mgi Jnum | J:313305 |
| Mgi Id | MGI:6705233 | Doi | 10.1007/s00109-019-01865-y |
| Citation | Amado T, et al. (2020) MicroRNA-181a regulates IFN-gamma expression in effector CD8(+) T cell differentiation. J Mol Med (Berl) 98(2):309-320 |
| abstractText | CD8(+) T cells are key players in immunity against intracellular infections and tumors. The main cytokine associated with these protective responses is interferon-gamma (IFN-gamma), whose production is known to be regulated at the transcriptional level during CD8(+) T cell differentiation. Here we found that microRNAs constitute a posttranscriptional brake to IFN-gamma expression by CD8(+) T cells, since the genetic interference with the Dicer processing machinery resulted in the overproduction of IFN-gamma by both thymic and peripheral CD8(+) T cells. Using a gene reporter mouse for IFN-gamma locus activity, we compared the microRNA repertoires associated with the presence or absence of IFN-gamma expression. This allowed us to identify a set of candidates, including miR-181a and miR-451, which were functionally tested in overexpression experiments using synthetic mimics in peripheral CD8(+) T cell cultures. We found that miR-181a limits IFN-gamma production by suppressing the expression of the transcription factor Id2, which in turn promotes the Ifng expression program. Importantly, upon MuHV-4 challenge, miR-181a-deficient mice showed a more vigorous IFN-gamma(+) CD8(+) T cell response and were able to control viral infection significantly more efficiently than control mice. These data collectively establish a novel role for miR-181a in regulating IFN-gamma-mediated effector CD8(+) T cell responses in vitro and in vivo. |
