An aging-susceptible circadian rhythm controls cutaneous antiviral immunity.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37725438.
- Also identified by DOI 10.1172/jci.insight.171548 and PMC identifier 10619492.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced levels of antiviral proteins (AVPs) and circadian regulators, including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin, and such circadian control of AVPs was diminished by disruption of immune cell IL-27 signaling and deletion of Bmal1/Clock genes in mouse skin, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment with the circadian-enhancing agents nobiletin and SR8278 reduced infection of herpes simplex virus 1 in epidermal explants and human keratinocytes in a BMAL1/CLOCK-dependent manner. Circadian-enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.
Medical subject headings
- ARNTL Transcription Factors
- Circadian Rhythm