lncRNAs in T lymphocytes: RNA-regulation at the heart of the immune response

Genome-wide analyses in the last decade have uncovered the presence of a large number of long non-protein-coding transcripts which show highly tissue- and state-specific expression patterns. High throughput sequencing analyses in diverse subsets of immune cells have revealed a complex and dynamic expression pattern for these long non-coding RNAs (lncRNAs) which correlate with the functional states of immune cells. While the vast majority of lncRNAs expressed in immune cells remain unstudied, functional studies performed on a small subset have indicated that their state-specific expression pattern frequently has a regulatory impact on the function of immune cells. In vivo and in vitro studies have pointed to the involvement of lncRNAs in a wide variety of cellular processes including both the innate and adaptive immune response through mechanisms ranging from epigenetic and transcriptional regulation to sequestration of functional molecules in subcellular compartments. This review will mainly focus on the role of lncRNAs in CD4+ and CD8+ T cells, which play pivotal roles in adaptive immunity. While lncRNAs play important physiological roles in lymphocytic response to antigenic stimulation, differentiation into effector cells and secretion of cytokines, their dysregulated expression can promote or sustain pathological states such as autoimmunity, chronic inflammation, cancer and viremia. This, together with their highly cell type-specific expression patterns, makes lncRNAs ideal therapeutic targets and underscores the need for additional studies into the role of these understudied transcripts in adaptive immune response.