Cannabinoid receptors (CBR) 1 and 2 have been implicated in keratinocyte differentiation/proliferation. How CB receptors affect epidermal permeability barrier and stratum corneum structure and function remains unclear. Permeability barrier abrogation was induced by sequential tape-stripping of the SC and assessed in both CB1R and CB2R knockout (-/-) mice in comparison with wild-type (+/+) littermates. Absence of CB1R delays permeability barrier recovery, while the latter was found to be accelerated in CB2R -/- mice. While increased lamellar body (LB) secretion is observed in CB2R -/- mice accounting for the enhanced recovery, CB1R -/- animals display strong alterations in lipid bilayer structures. Markers for epidermal differentiation (i.e. filaggrin, loricrin and involucrin) and terminal differentiation (i.e. TUNEL assay and caspase-14 activation) were respectively decreased and increased in CB1R and CB2R -/- mice. Surprisingly, CB1R agonist treatment of human cultured keratinocytes increases mRNA of p21 and cytokeratin 1 and 10 and decreases cyclin D1 but protein levels remained unchanged. Such paradox could partially be explained by the increase in non-phosphorylated-4E-BP1, an inhibitor of mRNA translation, following CB1R agonist treatment. Altogether, these observations put forward the importance and the complexity of cannabinoid signalling for the regulation of permeability barrier and epidermal differentiation.

Studies on sensitive skin pathophysiology in infants are challenging because most assessment methods require self-reporting of signs. In this study, we aimed to identify and characterize sensitive skin in children for the first time. A newly developed parent-reported questionnaire was used to recruit children with sensitive skin. This questionnaire was also tested on an adult group. Hydration, transepidermal water loss (TEWL), and inflammatory markers (cytokines, and polyunsaturated fatty acids (PUFAs)) were quantified. A total of 77 children and 20 adults (33 and 10 with sensitive skin, respectively) were recruited. The groups with sensitive skin had more clinical signs of skin dryness. Skin hydration was lower in children in the sensitive compared with the nonsensitive skin group. TEWL levels were similar between sensitive and nonsensitive subjects in both infant and adult groups. Sensitive skin exhibited higher levels of cytokines and proinflammatory PUFAs as well as lower levels of anti-inflammatory PUFAs. Sensitive skin syndrome was associated with normal skin barrier function but lower hydration in infants and children. The higher levels of proinflammatory markers suggest that sensitive skin is associated with low-level inflammation. It is hypothesized, for the first time, that PUFAs are involved in sensitive skin syndrome in infants.

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