In a new study published in Nature Immunology, Verykokakis and colleagues revealed that the transcription factor BCL-6 controls early development of innate-like T cells, including Natural Killer T (NKT) and Mucosal-Associated Invariant T (MAIT) cells. In contrast to T cells that are produced in the thymus as naïve cells, NKT and MAIT cells are pre-programmed to produce a vast amount of a range of cytokines immediately after infection. NKT cells acquire their unique features during a step-wise thymic differentiation process that enables the development of their poised phenotype. However, how this program is initiated is still unclear. The new study identified that BCL-6 is transiently expressed in the early stages of NKT differentiation and shapes the transcriptional and chromatin accessibility landscape to enable implementation of the NKT program in the late developmental stages. Importantly, inactivation of the Bcl6 gene led to premature disruption of NKT cell development and the generation of NKT cells that resembled conventional T cells. Therefore, the new study identified BCL-6 as novel key regulator of the innate-like phenotype in T cells. 


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