Flicr , a long noncoding RNA, modulates Foxp3 expression and autoimmunity.

A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) ( long intergenic noncoding RNA) is a negative regulator that tunes expression, resulting in a subset of Tregs with twofold- to fivefold-lower levels of FoxP3 protein. The impact of is particularly marked in conditions of IL-2 deficiency, and, conversely, IL-2 represses expression. neighbors in mouse and human genomes, is specifically expressed in mature Tregs, and acts only in It does not affect DNA methylation, but modifies chromatin accessibility in the conserved noncoding sequence 3 (CNS3)/Accessible region 5 (AR5) region of Like many lncRNAs, 's molecular effects are subtle, but by curtailing Treg activity, markedly promotes autoimmune diabetes and, conversely, restrains antiviral responses. This mechanism of FoxP3 control may allow escape from dominant Treg control during infection or cancer, at the cost of heightened autoimmunity.