Related Experiment Video
Updated: Nov 12, 2025
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
21.0K
Fasting-induced FOXO4 blunts human CD4+ T helper cell responsiveness
Kim Han1, Komudi Singh1,2, Matthew J Rodman1
1Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Nature Metabolism
|March 16, 2021
Summary
Intermittent fasting reduces inflammation by blunting CD4+ T helper cell responses. This immune modulation involves the FOXO4-FKBP5 pathway, offering new therapeutic insights.
Area of Science:
- Immunology
- Metabolic regulation
- Cellular signaling
Background:
- Intermittent fasting (IF) shows anti-inflammatory effects in conditions like asthma and rheumatoid arthritis.
- Mechanisms of fasting's immune-modulatory effects are not well understood.
- CD4+ T helper cells play a crucial role in immune responses and inflammation.
Discussion:
- Fasting significantly reduces CD4+ T helper cell activation and differentiation in humans.
- Transcriptomic analysis indicates longer fasting durations have a stronger impact on T helper cell biology.
- Bioinformatics identified the FOXO4-FKBP5 axis as a key fasting-responsive regulatory pathway.
Key Insights:
- Fasting blunts human CD4+ T helper cell responsiveness.
- The FOXO4-FKBP5 pathway regulates T helper cell cytokine production (TH1, TH17).
- FOXO4 and FKBP5 modulate mTORC1 signaling and STAT1/3 activation.
Outlook:
- The FOXO4-FKBP5 pathway represents a novel fasting-induced mechanism to dampen T helper cell activity.
- This discovery opens avenues for developing fasting-mimicking therapies for inflammatory diseases.
- Further research can explore targeting this pathway for immune modulation.
