PMID- 37725438
OWN - NLM
STAT- MEDLINE
DCOM- 20231103
LR  - 20240210
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 8
IP  - 20
DP  - 2023 Oct 23
TI  - An aging-susceptible circadian rhythm controls cutaneous antiviral immunity.
LID - 10.1172/jci.insight.171548 [doi]
LID - e171548
AB  - 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.
FAU - Kirchner, Stephen J
AU  - Kirchner SJ
AD  - Department of Dermatology.
AD  - Department of Molecular Genetics and Microbiology.
FAU - Lei, Vivian
AU  - Lei V
AD  - Department of Dermatology.
FAU - Kim, Paul T
AU  - Kim PT
AD  - Department of Dermatology.
FAU - Patel, Meera
AU  - Patel M
AD  - Department of Dermatology.
FAU - Shannon, Jessica L
AU  - Shannon JL
AD  - Department of Dermatology.
AD  - Department of Immunology.
FAU - Corcoran, David
AU  - Corcoran D
AD  - Duke Center for Genomic and Computational Biology.
FAU - Hughes, Dalton
AU  - Hughes D
AD  - Department of Neurobiology.
FAU - Waters, Diana K
AU  - Waters DK
AD  - Department of Neurobiology.
FAU - Dzirasa, Kafui
AU  - Dzirasa K
AD  - Department of Neurobiology.
AD  - Department of Psychiatry and Behavioral Sciences.
AD  - Department of Biomedical Engineering, and.
AD  - Department of Neurosurgery, Duke University, Durham, North Carolina, USA.
AD  - Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
FAU - Erdmann, Detlev
AU  - Erdmann D
AD  - Department of Surgery, Division of Plastic, Maxillofacial, and Oral Surgery, and.
FAU - Coers, Jorn
AU  - Coers J
AD  - Department of Molecular Genetics and Microbiology.
AD  - Department of Immunology.
FAU - MacLeod, Amanda S
AU  - MacLeod AS
AD  - Department of Dermatology.
AD  - Department of Molecular Genetics and Microbiology.
AD  - Department of Immunology.
FAU - Zhang, Jennifer Y
AU  - Zhang JY
AD  - Department of Dermatology.
AD  - Department of Pathology, Duke University, Durham, North Carolina, USA.
LA  - eng
GR  - R01 AI139207/AI/NIAID NIH HHS/United States
GR  - R01 AI139425/AI/NIAID NIH HHS/United States
GR  - R01 AR073858/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20231023
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (ARNTL Transcription Factors)
SB  - IM
UOF - bioRxiv. 2023 Apr 18;:. PMID: 37131751
MH  - Humans
MH  - Animals
MH  - Mice
MH  - Aged
MH  - *ARNTL Transcription Factors/genetics/metabolism
MH  - *Circadian Rhythm/physiology
MH  - Skin/metabolism
MH  - Aging
MH  - Keratinocytes/metabolism
PMC - PMC10619492
OTO - NOTNLM
OT  - Aging
OT  - Cellular immune response
OT  - Dermatology
OT  - Innate immunity
OT  - Skin
COIS- Conflict of interest: ASM has consulted for and received funds from Silab.
EDAT- 2023/09/19 18:43
MHDA- 2023/11/03 06:44
PMCR- 2023/10/23
CRDT- 2023/09/19 12:03
PHST- 2023/04/19 00:00 [received]
PHST- 2023/09/12 00:00 [accepted]
PHST- 2023/11/03 06:44 [medline]
PHST- 2023/09/19 18:43 [pubmed]
PHST- 2023/09/19 12:03 [entrez]
PHST- 2023/10/23 00:00 [pmc-release]
AID - 171548 [pii]
AID - 10.1172/jci.insight.171548 [doi]
PST - epublish
SO  - JCI Insight. 2023 Oct 23;8(20):e171548. doi: 10.1172/jci.insight.171548.