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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol

Published on: December 30, 2016

FOXP3 and the regulation of Treg/Th17 differentiation

Steven F Ziegler1, Jane H Buckner

  • 1Immunology, Benaroya Research Institute, Seattle, WA 98101, USA. sziegler@benaroyaresearch.org

Microbes and Infection
|April 18, 2009
PubMed

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.

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