| Summary: | Summary: Zbtb16 encodes the zinc-finger protein PLZF, which is often used as a lineage marker for innate-like T cells and is specifically required for the generation of invariant natural killer T (iNKT) cells in the thymus. Here, we report that not only PLZF expression itself but also the relative abundance of PLZF proteins plays critical roles in iNKT cell development. Utilizing a Zbtb16 hypomorphic allele, PLZFGFPCre, which produces PLZF proteins at only half of the level of the wild-type allele, we show that decreased PLZF expression results in a significant decrease in iNKT cell numbers, which is further associated with profound alterations in iNKT lineage choices and subset composition. These results document that there is a quantitative aspect of PLZF expression in iNKT cells, demonstrating that the availability of PLZF protein is a critical factor for both effective iNKT cell generation and subset differentiation. : iNKT cells are innate-like effector T cells that are produced in the thymus as three distinct subsets. Park et al. show that the relative abundance of the transcription factor PLZF drives subset differentiation of iNKT cells, revealing a quantitative aspect of PLZF expression in iNKT lineage choice. Keywords: IFN-γ, IL-4, iNKT cells, thymus, transcription factor
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