GATA3-Driven Th2 Responses Inhibit TGF-β1-Induced FOXP3 Expression And The Formation Of Regulatory T Cells

Main Category: Biology / Biochemistry
Article Date: 26 Dec 2007 - 17:00 PDT

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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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