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

Research output: Contribution to journalArticle

Researchers

  • Howell F. Moffett
  • Adam N.R. Cartwright
  • Hye Jung Kim
  • Jernej Godec
  • Jason Pyrdol
  • Tarmo Äijö
  • Gustavo J. Martinez
  • Anjana Rao
  • Jun Lu
  • Todd R. Golub
  • Harvey Cantor
  • Arlene H. Sharpe
  • Carl D. Novina
  • Kai W. Wucherpfennig

Research units

  • Harvard University
  • Rosalind Franklin University of Medicine and Science
  • Broad Institute
  • La Jolla Institute for Allergy and Immunology
  • Dana-Farber Cancer Institute

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.

Details

Original languageEnglish
Pages (from-to)791-799
Number of pages9
JournalNATURE IMMUNOLOGY
Volume18
Issue number7
Publication statusPublished - 20 Jun 2017
MoE publication typeA1 Journal article-refereed

ID: 14260482