Transcriptional regulation of the NKT cell lineage

► PLZF is the master transcription factor of the NKT cell lineage. ► PLZF is induced during thymic development by Egr2 downstream of TCR/NFAT signaling. ► PLZF directs acquisition of the innate-like effector program whereas Egr2 and other TCR signals/cosignals induce cell division. ► In addition to the major T-bethigh NKT1 subset, novel NKT sublineages include NKT2 and NKT17. ► Different mouse strains exhibit wide variations in the relative representation of NKT1, NKT2 and NKT17.