ArticleFrontiers in immunology2026
Frequency-selective thymic programming by early-life cold stress requires interferon regulatory factor 5.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Early-life environmental stressors can program immune development, but how the frequency of cold stress shapes thymic programming remains unknown. Methods: Developmentally matched (day 4, poikilothermic, yolk sac or milk dependent) zebrafish larvae and neonatal mice were exposed to two or four cycles of cold stress (termed 2× or 4× stress). Thymic development (zebrafish) and thymic T cell subsets (mice) were assessed, followed by influenza A virus (IAV) challenge in mice. Mechanisms were explored by RT-qPCR, western/dot blotting, and Results: In Conclusion: Early-life cold stress programs thymic immunity in a frequency-selective manner. Zebrafish genetics establish a causal requirement for IRF5, while mouse data show correlative changes in leptin signaling and IRF4/5. These findings highlight stress frequency as a key determinant of early-life immune programming and suggest potential windows for precise immunomodulation.
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