Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.
Document Type
Article
Publication Date
2007
Keywords
Base-Sequence, Cell-Differentiation, Cells-Cultured, GATA3-Transcription-Factor, Humans, Immunoglobulin-J-Recombination-Signal-Sequence-Binding, Mice-Inbred-C57BL, Mice-Knockout, Mice-Transgenic, Molecular-Sequence-Data, Receptors-Notch, Signal-Transduction, T-Lymphocytes-Helper-Inducer, Th1-Cells, Th2-Cells
First Page
89
Last Page
99
JAX Source
Immunity 2007 Jul; 27(1):89-99.
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.
Recommended Citation
Amsen D,
Antov A,
Jankovic D,
Sher A,
Radtke F,
Souabni A,
Busslinger M,
McCright B,
Gridley T,
Flavell RA.
Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch. Immunity 2007 Jul; 27(1):89-99.