Circadian control of interferon-sensitive gene expression in murine skin

Proceedings of the National Academy of Sciences of the United States of America
Elyse Noelani GreenbergBogi Andersen

Abstract

The circadian clock coordinates a variety of immune responses with signals from the external environment to promote survival. We investigated the potential reciprocal relationship between the circadian clock and skin inflammation. We treated mice topically with the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) to activate IFN-sensitive gene (ISG) pathways and induce psoriasiform inflammation. IMQ transiently altered core clock gene expression, an effect mirrored in human patient psoriatic lesions. In mouse skin 1 d after IMQ treatment, ISGs, including the key ISG transcription factor IFN regulatory factor 7 (Irf7), were more highly induced after treatment during the day than the night. Nuclear localization of phosphorylated-IRF7 was most prominently time-of-day dependent in epidermal leukocytes, suggesting that these cell types play an important role in the diurnal ISG response to IMQ. Mice lacking Bmal1 systemically had exacerbated and arrhythmic ISG/Irf7 expression after IMQ. Furthermore, daytime-restricted feeding, which affects the phase of the skin circadian clock, reverses the diurnal rhythm of IMQ-induced ISG expression in the skin. These results suggest a role for the circadian clock, driven by BMAL1, as a negativ...Continue Reading

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Citations

Jun 2, 2020·Frontiers in Immunology·Shan ChenJennifer J Loros
Dec 30, 2020·The Journal of Experimental Medicine·Miguel Palomino-Segura, Andrés Hidalgo
Nov 25, 2020·International Journal of Molecular Sciences·Stephen KirchnerAmanda S MacLeod
Dec 2, 2020·The Journal of Investigative Dermatology·Patrick-Simon Welz
Jul 3, 2021·International Journal of Molecular Sciences·Janet E LubovMichael G Kemp
Jul 13, 2021·Experimental Dermatology·Mahendran Chinnappan, Tamia A Harris-Tryon
Sep 22, 2021·International Reviews of Immunology·Xu-Li FanPei-Yao Lin
Sep 19, 2021·FEBS Letters·Junyan DuanBogi Andersen
Oct 2, 2021·The Journal of Clinical Investigation·Anna B FishbeinPhyllis C Zee

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Datasets Mentioned

BETA
GSE63980

Methods Mentioned

BETA
nuclear translocation
biopsies
RNA-seq
fluorescence-activated cell sorting
Protein
Flow cytometry
scRNA-seq

Software Mentioned

IDEAS
Plier
DAVID
Seurat R package
GSEA
ImageStream

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