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FOXP3 and the regulation of Treg/Th17 differentiation

Ziegler SF, Buckner JH2009Microbes and InfectionReview
10.1016/j.micinf.2009.04.002PubMedFree full text
Immune/Innate

Abstract

CD4 T cell lineages are marked by the signature transcription factor each lineage expresses. For example, regulatory T cells (Tregs) are characterized by expression of FOXP3, which is either induced during thymic development for natural Tregs (nTregs), or in the periphery in the presence of TGF-beta and retinoic acid for induced Tregs (iTreg). Interestingly, recent work has shown that the signature transcription factor for Th17 cells, RORgammat, is also induced by TGF-beta, thus linking the differentiation of the Treg and Th17 lineages. In the absence of a second signal from a proinflammatory cytokine, FOXP3 can inhibit RORgammat function and drive Treg differentiation. However, when the cell also receives a signal from a proinflammation cytokine (e.g., IL-6), FOXP3 function is inhibited and the Th17 differentiation pathway is induced. Therefore, it is the balance between FOXP3 and RORgammat function that determines CD4 T cell fate and the type of immune response that will be generated.

Key Biomarkers

Foxp3IL-6RORγtTGF-beta

Cited By (3)

  • Regulation of the T helper cell type 2 (Th2)/T regulatory cell (Treg) balance by Il-4 and STAT6Journal of Leukocyte Biology · 2010
  • Nature and nurture in Foxp3 (+) regulatory T cell development, stability, and functionHuman Immunology · 2012
  • Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspectiveNature reviews. Immunology · 2009

References (5)

  • Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3The Journal of Experimental Medicine · 2003
  • A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responsesNature Immunology · 2008
  • A Role for TGF-β in the Generation and Expansion of CD4+CD25+ Regulatory T Cells from Human Peripheral BloodThe Journal of Immunology · 2001

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