Transcriptional and epigenetic regulation of innate-like T lymphocyte development

Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell population that recognizes lipid antigens. Despite the monospecific nature of their T cell receptor, iNKT cells differentiate into stable sublineages during thymic development, prior to foreign antigen encounter. How iNKT cell subsets acquire and maintain their functional programs is a central question in innate lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT subsets has provided insights into the internal wiring of these subsets that defines their identity. Comparison of the iNKT transcriptional programs with those of other adaptive and innate lymphocyte lineages revealed common core regulatory circuits that may dictate effector functions. In this review, we summarize recent advances on the molecular mechanisms involved in iNKT cell development.