T Cell Factor-1 and β-catenin specifically and critically control the generation and function of T helper 2-type natural killer T cells (LYM7P.725)

Phenotypically and functionally heterogeneous natural killer T (NKT) cells develop from common thymocyte precursors. Transcriptional programs that regulate the development of different subsets of NKT cells remain to be delineated. In this report we demonstrate that transcription factors T cell factor (TCF)-1 and β-catenin direct the development of CD4+ T helper (Th)2-type, IL-4-producing NKT2 cells in the thymus without influencing the development of Th1-type NKT1 cells. NKT2 cells are significantly diminished in TCF1-deficient and β-catenin-deficient mice and are increased in mice with enforced expression of β-catenin. Increased NKT2 cells in mice with enforced expression of β-catenin are functional and produce increased cytokines that exacerbate the development of IL-25-dependent airway hypersensitivity.