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Frequency-selective thymic programming by early-life cold stress requires interferon regulatory factor 5
Shengnan Wang1, Liyuan Li1, Haokun Li1
1Medical Basic Research Innovation Center of Airway Disease in North China and Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, China.
Frontiers in Immunology
|July 30, 2026
Summary
Early-life cold stress frequency selectively programs the thymus. Two cold stress cycles benefit immune responses, while four cycles impair them, with IRF5 playing a key role.
Area of Science:
- Immunology
- Developmental Biology
- Environmental Health
Background:
- Early-life environmental stressors can influence immune system development.
- The impact of cold stress frequency on thymic programming is not well understood.
Purpose of the Study:
- To investigate how the frequency of cold stress impacts thymic immune programming in early life.
- To explore the underlying molecular mechanisms in zebrafish and mice.
Main Methods:
- Zebrafish larvae and neonatal mice were exposed to two or four cycles of cold stress.
- Thymic development and T cell subsets were analyzed.
- Gene expression (IRF4/5, leptin signaling) and immune challenge (influenza A virus) were assessed.
Main Results:
- Two cold stress cycles enhanced thymic T cell expression and improved survival in mice, while four cycles impaired thymic development and offered no acute protection.
- Zebrafish studies revealed frequency-dependent effects on thymic development, linked to IRF5 and leptin signaling pathways.
- IRF5 was identified as crucial for the frequency-selective cold stress response in zebrafish.
Conclusions:
- Early-life cold stress frequency critically determines thymic immune programming outcomes.
- IRF5 is causally involved in this frequency-selective response, as shown in zebrafish.
- Findings suggest specific windows for immunomodulation based on stress frequency.
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