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: In the liver and spleen of Lef1Δ/Δ mice, the frequency of CD4+ iNKT cells was reduced and a novel population of CD8+ iNKT cells emerged (Fig. 6, A and B). The loss of CD4 and increased expression of CD8 on liver iNKT cells was intrinsic to the Lef1Δ/Δ cells as determined in mixed bone marrow chimeras (Fig. 6, C and D). We examined the expression of Th-POK in Lef1Δ/Δ splenic iNKT cells because Th-POK has been implicated as a GATA3 target that represses Cd8 expression in these cells (Wang et al., 2010), and LEF1 expression was correlated with both GATA3 and Th-POK (Fig. 5 B). We found that Th-POK expression was reduced in the absence of LEF1, particularly in the CD8-expressing iNKT cells (Fig. 6 E). Therefore, similar to GATA3, LEF1 was required for proper expression of Th-POK and promoted the development of CD4+ cells while preventing the expression of CD8 on peripheral iNKT cells.
Affiliation: Committee on Immunology, Committee on Molecular Pathogenesis and Molecular Medicine, and Department of Pathology, The University of Chicago, Chicago, IL 60637.