The airway epithelium plays a crucial role in respiratory defense by regulating cellular composition and related functions to maintain pulmonary homeostasis. This study investigates the impact of temperature variations (33°C and 37°C) on cellular differentiation, mucociliary func
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The airway epithelium plays a crucial role in respiratory defense by regulating cellular composition and related functions to maintain pulmonary homeostasis. This study investigates the impact of temperature variations (33°C and 37°C) on cellular differentiation, mucociliary function, and host defense responses of human primary bronchial and nasal epithelial cells (hPBECs and hPNECs) cultured at the air-liquid interface. A reduction of well-differentiated cell cultures from 37°C to 33°C
significantly increased goblet cell-related gene expression (MUC5AC) while decreasing ciliated cell-related gene expression (FOXJ1). Mucociliary clearance was generally impaired at 33°C, with ciliated cells displaying less organized ciliary alignment; however, donor variability made it challenging to establish consistent trends. Furthermore, cultures maintained at 33°C exhibited an enhanced antiviral response to Poly(I:C), as indicated by increased IFNL gene expression in both bronchial and nasal epithelial cells. In contrast, temperature had no effect on the inflammatory response to whole cigarette smoke in bronchial cultures but attenuated the oxidative stress response in nasal cultures,
as evidenced by reduced HMOX1 expression at 33°C. Analysis of Notch signaling revealed no significant alterations in the expression of key target genes (HES1, HEY1), with the exception of a transient decrease in HEY2 at 33°C, suggesting complex regulatory interactions. These findings
support the hypothesis that the temperature gradient along the airway tree influences the spatial distribution of airway epithelial cells, with potential implications for intervention with airway remodeling in chronic lung diseases, such as asthma and chronic obstructive pulmonary disease.
However, further studies are needed to confirm these results and explore their clinical relevance.