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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.

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


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.

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