Related Experiment Video

Updated: Jun 22, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
08:20

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 inhibits activation-induced NFAT2 expression in T cells thereby limiting effector cytokine expression

Troy R Torgerson1, Anna Genin, Chunxia Chen

  • 1Department of Pediatrics, University of Washington School of Medicine and Children's Hospital, Seattle, WA 98109, USA. troy.torgerson@seattlechildren's.org

Journal of Immunology (Baltimore, Md. : 1950)
|July 1, 2009
PubMed

Insights

Forkhead box protein 3 (FOXP3) represses NFAT2 transcription, a key mechanism for regulatory T cell (TREG) function. This FOXP3-NFAT2 interaction is crucial for maintaining self-tolerance and suppressing inflammatory responses.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Forkhead DNA-binding protein FOXP3 is essential for regulatory T cell (TREG) development and function.
  • TREGs are critical for maintaining self-tolerance.
  • FOXP3's mechanism of action in repressing cytokine gene transcription is under investigation.

Purpose of the Study:

  • To elucidate the specific molecular targets and mechanisms by which FOXP3 exerts its transcriptional repression.
  • To investigate the role of NFAT2 as a target of FOXP3 in TREG function.
  • To understand how FOXP3-mediated repression of NFAT2 contributes to the anergic phenotype of TREGs.

Main Methods:

  • Utilized novel cell lines with inducible expression of wild-type or mutant FOXP3.
  • Performed quantitative analysis of NFAT2 promoter activity and protein expression.
  • Conducted chromatin immunoprecipitation (ChIP) assays to assess FOXP3 and NFAT1 binding to the NFAT2 promoter.
  • Investigated the effect of ectopic NFAT2 expression on IL-2 production in FOXP3(+) TREGs.

Main Results:

  • Identified NFAT2 as an early transcriptional target of FOXP3.
  • Demonstrated significant suppression of NFAT2 promoter activity by FOXP3.
  • Observed markedly diminished NFAT2 protein expression in activated FOXP3(+) TREGs compared to T cells lacking FOXP3.
  • Showed that FOXP3 competes with NFAT1 for binding to the NFAT2 promoter.
  • Found that ectopic NFAT2 expression partially restored IL-2 expression in FOXP3(+) TREGs.

Conclusions:

  • FOXP3 directly represses the transcription of NFAT2, contributing to the anergic state of TREGs.
  • FOXP3's antagonism of NFAT2 activity is a key mechanism for maintaining self-tolerance.
  • FOXP3 may regulate sustained inflammatory gene expression by suppressing inducible NFAT2 transcription, impacting broader immune responses.

More Related Videos

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation15:33

Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation

Published on: August 13, 2013

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...