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

Cited 27 time in Web of Science Cited 28 time in Scopus

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

Issue Date
Cell Press
Cell Reports, Vol.27 No.9, pp.2548-2557.e4
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, PLZF GFPCre, 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.
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