Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell Generation.

Joo-Young Park, Devon T DiPalma, Juntae Kwon, Juliet Fink, Jung-Hyun Park

Cell reports 2019 May 28

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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. Published by Elsevier Inc.

Citation

Joo-Young Park, Devon T DiPalma, Juntae Kwon, Juliet Fink, Jung-Hyun Park. Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell Generation. Cell reports. 2019 May 28;27(9):2548-2557.e4