Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1) Plays a Major Role in Low Temperature-Mediated Skin Barrier Dysfunction: Potential Implications for Atopic Dermatitis and Food Allergy

Multiple studies have reported that babies born in the fall and winter are at increased risk for developing atopic dermatitis and food allergy. We found that these seasons are associated with extreme fluctuations in temperature. It has been suggested that activation of transient receptor potential cation channel subfamily V member 1 (TRPV1) by various factors such as temperature is associated with skin temperature sensing. Primary human epidermal keratinocytes (HEKs) were cultured at different temperatures to study their effects on expression of epidermal barrier proteins. HEKs were transfected with TRPV1 or signal transducer and activator of transcription (STAT)-3 siRNA, followed by incubation at 25oC or 37oC for various time periods. Gene expression of TRPV1, epidermal barrier proteins, and keratinocyte-derived cytokines were evaluated by RT-PCR. Organotypic skin equivalents were generated using HEKs transfected with TRPV1 or control siRNA and grown at 25oC or 37oC. Transepidermal water loss (TEWL) was measured, and levels of epidermal barrier proteins were evaluated. Filaggrin (FLG), loricrin (LOR), and corneodesmosin gene expression, but not keratin (KRT)-1 and KRT-10 expression was downregulated in HEKs incubated at 25oC. TRPV1 silencing increased the calcium influx (keratinocyte differentiation signal) and enhanced the expression of epidermal differentiation proteins. Moreover, low temperature-mediated inhibition of FLG and LOR was recovered, and TEWL was decreased in organotypic skin transfected with TRPV1siRNA. IL-1beta and TSLP induced by low temperature inhibited FLG expression in keratinocytes through the TRPV1/STAT-3 pathway. Low temperature downregulates epidermal barrier proteins and causes skin barrier dysfunction through TRPV1.