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Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell
Joo-Young Park1, Devon T DiPalma2, Juntae Kwon2
1Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1360, USA; Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, 101 Daehakno, Jongno-gu, Seoul 03080, South Korea.
Abstract:
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.
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