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Nat Immunol. 2017 Jul;18(7):791-799. doi: 10.1038/ni.3755. Epub 2017 May 22.

The microRNA miR-31 inhibits CD8+ T cell function in chronic viral infection.

Author information

1
Department of Cancer Immunology &Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
2
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
3
Department of Information and Computer Science, Aalto University School of Science, Aalto, Finland.
4
La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
5
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Abstract

During infection, antigen-specific T cells undergo tightly regulated developmental transitions controlled by transcriptional and post-transcriptional regulation of gene expression. We found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor (TCR) in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus (LCMV) clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease. This disease phenotype was explained by the presence of larger numbers of cytokine-secreting LCMV-specific CD8+ T cells in miR-31-deficent mice than in wild-type mice. Mechanistically, miR-31 increased the sensitivity of T cells to type I interferons, which interfered with effector T cell function and increased the expression of several proteins related to T cell dysfunction during chronic infection. These studies identify miR-31 as an important regulator of T cell exhaustion in chronic infection.

PMID:
28530712
PMCID:
PMC5753758
DOI:
10.1038/ni.3755
[Indexed for MEDLINE]
Free PMC Article

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