341 Age and circadian regulation of cutaneous innate antimicrobial immunity

Neonates and elderly are at increased risk for skin viral and bacterial infections that have the potential to cause systemic malaise and death. Notably, under healthy conditions, and predominantly previously studied in adult skin, a natural antimicrobial defense program protects the host against microbial infections. Interestingly, newborns and elderly have immature diurnal circadian rhythms. Unknown to us is whether age and/or circadian rhythm regulate innate antimicrobial immunity in the skin. Here, we aimed to address the question whether an immature perinatal and dysregulated circadian clock suppresses innate antimicrobial peptide and protein expression, which consequently allows for predisposition to infections. We hypothesized that age-related maturation of the daily circadian rhythm via CLOCK/BMAL1 facilitates transcriptional regulation of innate antimicrobial host defense molecules in the skin. Innate antimicrobial peptides and proteins (AMPs), including antiviral proteins, play a pivotal role in innate immune defense system to protect against invading pathogens. AMPs are expressed in most barrier tissues, including the skin. Here, we show that many cutaneous AMP mRNAs are not expressed at birth, but their expression induction instead coincide with maturation of the circadian clock in mice. We also show using ex vivo studies in adult human skin that homeostatic AMP mRNA expression changes with age. Our findings indicate that AMP expression varies with age in human and murine skin, possibly in relation to altered expression of CLOCK/BMAL1.