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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

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YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity

Soo Seok Hwang1,2,3, Sung Woong Jang1, Min Kyung Kim1

  • 1Department of Life Science, Sogang University, 35 Baekbeom-ro, Seoul 121-742, Korea.

Nature Communications
|February 20, 2016
PubMed

Insights

The transcription factor YY1 negatively regulates regulatory T (Treg) cells, crucial for immune balance. Increased YY1 impairs Treg cell function by blocking Foxp3, impacting immune homeostasis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Regulatory T (Treg) cells maintain immune homeostasis.
  • The transcription factor Foxp3 is critical for Treg cell function.
  • Mechanisms of Foxp3's negative regulation are not well understood.

Purpose of the Study:

  • To investigate the role of YY1 in Treg cell differentiation and function.
  • To elucidate the molecular mechanisms by which YY1 affects Foxp3 expression and Treg cell activity.

Main Methods:

  • Quantitative analysis of YY1 expression in T(reg) versus T(conv) cells.
  • Overexpression studies of YY1 in Treg cells.
  • Assessment of Treg cell suppressive function in vitro and in vivo (dextran sulfate-induced colitis model).
  • Chromatin immunoprecipitation assays to study YY1 binding to the Foxp3 locus and target genes.

Main Results:

  • YY1 expression is lower in Treg cells compared to conventional T cells.
  • YY1 overexpression reduces Foxp3 expression and Treg cell suppressive function.
  • YY1 levels increase in Treg cells during inflammation (colitis model), correlating with decreased suppressor activity.
  • YY1 inhibits Smad3/4 binding and chromatin remodeling at the Foxp3 locus.
  • YY1 physically interacts with Foxp3 and binds to Foxp3 target genes, disrupting their expression.

Conclusions:

  • YY1 acts as a negative regulator of Treg cell differentiation and function.
  • YY1 inhibits Treg cell activity by interfering with Foxp3 expression and downstream signaling.
  • Targeting YY1 may offer a therapeutic strategy for immune-related disorders.

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