GATA3-Driven Th2 Responses Inhibit TGF-ОІ1-Induced FOXP3 Expression And The Formation Of Regulatory T Cells

Immune responses against foreign bodies are driven by specialized T-cells
whose numbers expand upon recognition of antigen found on professional
antigen-presenting cells. The subsequent maturation process involves the
differentiation of certain T-cell phenotypes such as pro-inflammatory
cells
(Th1, Th2, Th17) or regulatory T-cells (Tregs), which serve to keep the
immune response in check. The current study focuses on the role of two
key
transcription factors, FOXP3 and GATA3, in controlling the commitment of
these cells.

Published this week in the open-access journal PLoS Biology,
Pierre-Yves Mantel, Carsten Schmidt-Weber, and colleagues demonstrate that
the Th2 cytokine IL-4 inhibits the induction of FOXP3 and thus the
generation of inducible Tregs. They show that IL-4-induced GATA3 mediates
FOXP3-inhibition by directly binding to a GATA-element in the FOXP3
promoter. They also hypothesize that therapeutic agents aimed at
neutralizing IL-4 could be a novel strategy to facilitate inducible
Treg-generation
and thus promotion of tolerance in allergies and other Th2-dominated
diseases.



Citation: Mantel PY, Kuipers H, Boyman O, Rhyner C, Ouaked N, et al.
(2007) GATA3-driven Th2 responses inhibit TGF-b1-induced FOXP3 expression
and
the formation of
regulatory T cells. PLoS Biol 5(12): e329.
doi:10.1371/journal.pbio.0050329

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