Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells.

Despite extensive mapping of long noncoding RNAs in immune cells, their function in vivo remains poorly understood. In this study, we identify over 100 long noncoding RNAs that are differentially expressed within 24 h of Th1 cell activation. Among those, we show that suppression of is a hallmark of CD4 T cell activation, but its complete deletion results in more potent immune responses to infection. This is because Th1 and Th2 cells express lower levels of the immunosuppressive cytokine IL-10. In vivo, the reduced CD4 T cell IL-10 expression in mice underpins enhanced immunity and pathogen clearance in experimental visceral leishmaniasis () but more severe disease in a model of malaria ( AS). Mechanistically, regulates IL-10 through enhancing expression of Maf, a key transcriptional regulator of Maf expression correlates with in single Ag-specific Th cells from AS-infected mice and is downregulated in Th1 and Th2 cells. The RNA is responsible for these effects, as antisense oligonucleotide-mediated inhibition of also suppresses Maf and IL-10 levels. Our results reveal that through promoting expression of the Maf/IL-10 axis in effector Th cells, is a nonredundant regulator of mammalian immunity.