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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Transcriptional control of regulatory T cell development and function
1Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Trends in Immunology
|September 11, 2013
Summary
Regulatory T (Treg) cells require specific antigen stimulation to express the key transcription factor, forkhead box P3 (Foxp3). This process involves balancing T cell receptor signals and Akt signaling for proper Treg cell differentiation and function.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Regulatory T (Treg) cells are crucial for immune homeostasis, differentiating from thymocytes or peripheral T cells.
- Treg cell differentiation involves the induction of the transcription factor forkhead box P3 (Foxp3) and a specific epigenome.
- This differentiation is influenced by host and environmental cues.
Purpose of the Study:
- To elucidate the molecular mechanisms controlling Treg cell lineage commitment.
- To understand the role of transcription factors and signaling pathways in Treg cell differentiation.
- To investigate how extracellular signals modulate Treg cell development.
Main Methods:
- Analysis of transcription factor induction during Treg cell differentiation.
- Investigation of T cell receptor (TCR) signaling pathways, including NF-κB and Foxo.
- Examination of Akt signaling pathways and their impact on Foxo1 nuclear retention.
Main Results:
- Intermediate antigen stimulation is necessary for Foxp3 induction, involving both TCR-activated (NF-κB) and TCR-inhibited (Foxo) transcription factors.
- Treg cell differentiation is linked to attenuated Akt signaling.
- Attenuated Akt signaling leads to enhanced nuclear retention of Foxo1, which is essential for Treg cell function.
Conclusions:
- Treg cell lineage commitment is a complex process influenced by genetic and epigenetic factors.
- Transcriptional programs responding to extracellular signals play a significant role in modulating Treg cell differentiation.
- The interplay between TCR signaling, Akt pathway, and transcription factors like Foxp3 and Foxo1 is critical for Treg cell development.
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