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Updated: May 18, 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

Synergy between IL-6 and TGF-β signaling promotes FOXP3 degradation

Zhimei Gao1, Yayi Gao, Zhiyuan Li

  • 1The Bioengineering Graduate Program, School of Life Sciences, Fudan University, Shanghai, 200433, China.

International Journal of Clinical and Experimental Pathology
|September 15, 2012
PubMed

Insights

Inflammation reduces FOXP3 protein levels by promoting its degradation. This study reveals that combined TGF-β and IL-6 treatments trigger FOXP3 protein breakdown, offering a target for modulating regulatory T cell function.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • FOXP3 is a key transcription factor for regulatory T cell (Treg) development and function.
  • Mechanisms of FOXP3 downregulation in inflammatory conditions are not fully understood.

Purpose of the Study:

  • To investigate how FOXP3 protein levels are regulated post-translationally under inflammatory conditions.
  • To elucidate the role of transforming growth factor-beta (TGF-β) and IL-6 in FOXP3 regulation.

Main Methods:

  • Utilized an FOXP3 overexpression model.
  • Treated cells with a combination of TGF-β and IL-6 (IL-6/TGF-β).
  • Assessed FOXP3 mRNA stability and protein degradation.
  • Employed the proteasome inhibitor MG132.

Main Results:

  • IL-6/TGF-β treatment synergistically downregulated FOXP3 protein, independent of mRNA stability.
  • This downregulation was mediated by enhanced FOXP3 protein degradation.
  • IL-6/TGF-β upregulated IL-6 receptor (IL-6R) expression.
  • MG132 treatment inhibited IL-6/TGF-β-induced FOXP3 protein reduction.

Conclusions:

  • The inflammatory microenvironment, via IL-6/TGF-β signaling, promotes FOXP3 degradation at the post-translational level.
  • Targeting FOXP3 degradation presents a potential strategy for modulating Treg activity during inflammation.
Keywords:
FOXP3IL-6TGF-βTreginstabilityproteasome

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