1. Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.
- Author
-
Amsen D, Antov A, Jankovic D, Sher A, Radtke F, Souabni A, Busslinger M, McCright B, Gridley T, and Flavell RA
- Subjects
- Animals, Base Sequence, Cells, Cultured, GATA3 Transcription Factor biosynthesis, GATA3 Transcription Factor physiology, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein deficiency, Immunoglobulin J Recombination Signal Sequence-Binding Protein genetics, Immunoglobulin J Recombination Signal Sequence-Binding Protein physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Molecular Sequence Data, Signal Transduction immunology, T-Lymphocytes, Helper-Inducer metabolism, Th1 Cells cytology, Th1 Cells immunology, Th1 Cells metabolism, Th2 Cells cytology, Th2 Cells immunology, Th2 Cells metabolism, Cell Differentiation immunology, GATA3 Transcription Factor metabolism, Receptors, Notch physiology, T-Lymphocytes, Helper-Inducer cytology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch.
- Published
- 2007
- Full Text
- View/download PDF