Non-optimal temperature effects on respiratory epithelial cells in vitro : Relevance to climate change

Non-optimal ambient temperature is a critical environmental stressor linked to adverse respiratory outcomes under climate change, yet the underlying cellular mechanisms remain poorly defined. This review synthesizes in vitro evidence regarding thermal stress effects on the respiratory epithelium. Through a comprehensive search of the Web of Science Core Collection, we identified 82 eligible studies investigating epithelial responses to heat or cold. Ciliary activity is temperature-sensitive, peaking at approximately 37 °C. Thermal stress disrupts epithelial homeostasis by altering barrier integrity, cytoskeletal mechanics, and cellular differentiation. Key molecular sensors, including transient receptor potential vanilloid 4 and melastatin 8 channels, heat shock factor 1, and cold-inducible RNA-binding protein, emerge as mediators of mucin hypersecretion and inflammatory signaling. Notably, cooler temperatures in the upper airways are associated with enhanced viral replication (e.g., SARS-CoV-2 and rhinovirus), partly through altered interferon-mediated antiviral responses. Furthermore, low temperature consistently suppresses energy-dependent uptake and transepithelial transport of macromolecules and nanoparticles. Thermal conditions also modulate epithelial susceptibility to other stressors, including oxidants, pollutants, and non-optimal humidity. Airway-relevant or clinically plausible thermal deviations, including mild upper-airway cooling and febrile-range warming, can alter epithelial homeostasis, immune responses, and host–pathogen interactions. By contrast, extreme in vitro thermal conditions primarily serve as mechanistic stress models that help define the thermal dependence and functional limits of epithelial transport, metabolism, and injury responses. These findings underscore the need to interpret in vitro thermal effects according to anatomical location, breathing pattern, and physiological plausibility when relating them to real-world climate exposures.