The microRNA miR-31 inhibits CD8 T cell function in chronic viral infection.
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.
|Year of Publication
|PubMed Central ID
T32 AI007386 / AI / NIAID NIH HHS / United States
R01 AI040127 / AI / NIAID NIH HHS / United States
P01 AI056299 / AI / NIAID NIH HHS / United States
R01 CA140986 / CA / NCI NIH HHS / United States
S10 RR027366 / RR / NCRR NIH HHS / United States
R01 CA173750 / CA / NCI NIH HHS / United States
R01 DK102165 / DK / NIDDK NIH HHS / United States