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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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The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells

Takashi Sekiya1, Ikkou Kashiwagi, Naoko Inoue

  • 1Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.

Nature Communications
|April 7, 2011
PubMed

Insights

Nuclear receptor subfamily 4 group A member 2 (Nr4a2) regulates regulatory T cells (Tregs) by controlling Foxp3 expression. This maintains immune homeostasis and prevents inflammatory diseases like colitis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Regulatory T cells (Tregs) are crucial for immune homeostasis.
  • The transcription factor Foxp3 defines Treg lineage and function.
  • Mechanisms of Foxp3 induction and maintenance are not fully understood.

Purpose of the Study:

  • To investigate the role of Nr4a2 in Treg function.
  • To elucidate the molecular mechanisms by which Nr4a2 regulates Foxp3.
  • To determine the in vivo relevance of Nr4a2 in immune regulation and disease.

Main Methods:

  • Investigated Nr4a2 binding to Foxp3 regulatory regions.
  • Assessed histone modifications mediated by Nr4a2.
  • Examined the effects of Nr4a2 expression on T cell function in vitro and in vivo.
  • Utilized Nr4a2 deletion models in T cells to study colitis.

Main Results:

  • Nr4a2 directly targets Foxp3, mediating permissive histone modifications.
  • Ectopic Nr4a2 expression induces Treg-like suppressive activity and represses cytokines (IFN-γ, IL-2).
  • Nr4a2 deletion in T cells impairs Treg induction, promotes Th1 induction, exacerbates colitis, and reduces Treg suppressive function.

Conclusions:

  • Nr4a2 is essential for Treg induction, maintenance, and suppressive function.
  • Nr4a2 maintains T cell homeostasis by regulating Tregs and repressing aberrant Th1 induction.
  • Nr4a2 plays a critical role in preventing inflammatory conditions like colitis.

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