Temperature changes contribute to skin barrier dysfunction: potential implications for atopic dermatitis and food allergy

Children born in the fall are at increased risk for developing atopic dermatitis (AD) and food allergy (FA), two conditions associated with skin barrier dysfunction. During an analysis of meteorological data in Denver, we found that the most extreme 24-hour temperature fluctuations occur in the fall. This prompted us to evaluate the effect of temperature on epidermal differentiation and Ca2+ transport function of transient receptor potential vanilloid (TRPV) ion channels involved in skin temperature sensing. Human epidermal keratinocytes were Ca2+-differentiated for 3 days, followed by additional studies at various temperatures (25°C, 30°C, 37°C, 41°C). Gene expression levels of filaggrin (FLG) and TRPV1, TRPV2, TRPV3, TRPV4 were measured with RT-PCR. Real-time dynamics of intracellular Ca2+ influx was assessed in live keratinocytes by flow cytometry. Exposure of undifferentiated keratinocytes to increased Ca2+ (cell differentiation signal) triggered a rapid intracellular Ca2+ influx. Cells cultured at 25°C, 30°C and 41°C exhibited significant decreases in the peak amplitude of Ca2+ influx (p<0.05), as compared to the 37°C condition. FLG expression in differentiated keratinocytes was significantly decreased (p<0.001) in cells incubated at 25°C and 30°C as compared to the cells incubated at 37°C and 41°C. Gene expression of TRPV1 and TRPV4, but not TRPV2 and TRPV3, in differentiated keratinocytes were temperature-sensitive. Differential temperature exposures alter keratinocyte responses to the Ca2+ differentiation signal, as well as FLG and TRPV expression. Further mechanistic studies of TRPVs may provide insight into the effects of temperature on skin barrier dysfunction.