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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
PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors
Matthias Merkenschlager1, Harald von Boehmer
1Lymphocyte Development Group, Medical Research Council Clinical Sciences Centre, Imperial College London, London W12 0NN, UK. matthias.merkenschlager@csc.mrc.ac.uk
The Journal of Experimental Medicine
|July 7, 2010
Summary
Regulatory T (T reg) cell Foxp3 expression is induced by T cell receptor (TCR), IL-2, and TGF-beta signals. New findings reveal Foxo proteins drive Foxp3 expression, explaining PI3K signaling
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Regulatory T (T reg) cells are crucial for immune homeostasis.
- Foxp3 is a key transcription factor for T reg cell development and function.
- TCR, IL-2, and TGF-beta signaling pathways converge to regulate Foxp3 expression.
Purpose of the Study:
- To elucidate the role of Foxo proteins in Foxp3 regulation.
- To understand the integration of PI3K signaling in Foxp3 induction.
- To identify novel nuclear factors modulating Foxp3 expression.
Main Methods:
- Investigated the interaction between Akt, Foxo proteins, and Foxp3.
- Utilized molecular biology techniques to study gene expression.
- Analyzed signaling networks involving PI3K/Akt/mTOR pathways.
Main Results:
- Foxo proteins (Foxo1 and Foxo3a) were found to drive Foxp3 expression.
- Akt-mediated inactivation of Foxo proteins negatively regulates Foxp3.
- PI3K signaling negatively impacts Foxp3 expression via Akt-mediated Foxo inactivation.
Conclusions:
- Foxo proteins are novel positive regulators of Foxp3 expression.
- PI3K/Akt signaling negatively controls Foxp3 expression through Foxo inactivation.
- These findings expand the understanding of molecular mechanisms governing T reg cell differentiation.
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