The transcriptional programs of iNKT cells

Invariant natural killer T (iNKT) cells are innate T cells that express a semi-invariant T cell receptor (TCR) and recognize lipid antigens presented by CD1d molecules. As part of innate immunity, iNKT cells rapidly produce large amounts of cytokines after activation and regulate the function of innate and adaptive immune cells in antimicrobial immunity, tumor rejection and inflammatory diseases. Global transcriptional profiling has advanced our understanding of all aspects of iNKT cell biology. In this review, we discuss transcriptional analyses of iNKT cell development, functional subsets of iNKT cells, and global comparisons of iNKT cells to other innate and adaptive immune cells. Global transcriptional analysis revealed that iNKT cells have a transcriptional profile distinct from NK cells and MHC-restricted T cells, both during thymic development and in the periphery. The transcription factors EGR2 and PLZF (and microRNA like miR-150) are key regulators of the iNKT cell transcriptome during development. PLZF is one of several factors that control the homing and maintenance of organ-specific iNKT cell populations. As in MHC-restricted T cells, specific transcription factors are characteristic of functional subsets of iNKT cells, such as the transcription factor T-bet in the NKT1 subset. Exciting future directions for global transcriptional analyses include iNKT cells in disease models, diverse NKT cells and human studies.