Children born in the fall and winter are at increased risk for developing atopic dermatitis and food allergy. Because these seasons are associated with low temperatures, we hypothesized that exposure to low temperatures may compromise keratinocyte differentiation and contribute to skin barrier dysfunction.

We examined whether low temperature causes skin barrier dysfunction.

Primary human epidermal keratinocytes (HEK) were differentiated in 1.3 mmol CaCl₂ media and cultured at different temperatures. The cells were transfected with transient receptor potential cation channel subfamily V member 1 (TRPV1) or STAT3 small interfering RNA (siRNA) to examine the effects of these gene targets in HEK exposed to low temperature. Gene expression of TRPV1, epidermal barrier proteins, and keratinocyte-derived cytokines were evaluated. Organotypic skin equivalents were generated using HEK transfected with control or TRPV1 siRNA and grown at 25°C or 37°C. Transepidermal water loss (TEWL) and levels of epidermal barrier proteins were evaluated.

Filaggrin (FLG) and loricrin (LOR) expression, but not keratin (KRT)-1 and KRT-10 expression, was downregulated in HEK incubated at 25°C, while TRPV1 silencing increased intracellular Ca²⁺ influx (keratinocyte differentiation signal) and enhanced the expression of epidermal differentiation proteins. IL-1β and thymic stromal lymphopoietin induced by low temperature inhibited FLG expression in keratinocytes through the TRPV1/STAT3 pathway. Moreover, low temperature–mediated inhibition of FLG and LOR was recovered, and TEWL was decreased in organotypic skin transfected with TRPV1 siRNA.

TRPV1 is critical in low temperature–mediated skin barrier dysfunction. Low temperature exposure induced thymic stromal lymphopoietin, an alarmin implicated in epicutaneous allergen sensitization.