The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation.
Bottom Line: These cells acquire multiple effector fates during their thymic development that parallel those of CD4(+) T helper cells.LEF1 also directly augments expression of the effector fate-specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ.Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.
Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.Show MeSH
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Mentions: To better understand how LEF1 functioned, we examined LEF1 expression in cells at each stage of iNKT cell development. We used the β chain of the IL-2/15 receptor (CD122) to resolve ST3 iNKT cells because our mice were on the FVB/NJ background, which fails to express the classic NK cell marker NK1.1. CD122 expression was directly correlated with the ST3 transcription factor TBET, and CD44 and CD122 fractionated CD24lo iNKT cells into ST1 (CD44loCD122−), ST2 (CD44+CD122−), and ST3 (CD44+CD122+) cells (Fig. 2 A). We found that LEF1 was highly expressed in ST1 and ST2 cells and was absent from the majority of cells at ST3 (Fig. 2 B). LEF1 was also highly expressed in ST0 iNKT cells (Fig. 2 B). Therefore, LEF1 was expressed at the earliest stages of iNKT cell development.
Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.