Peer Reviewed

1

Document Type

Article

Publication Date

12-2017

Keywords

Molecular clock, Myeloid cells, CNS

Funder/Sponsor

This work was supported by Science Foundation Ireland (SFI) Principle Investigator Research Grant 11/PI/1036 and an SFI infrastructure grant (12/RI/2340) to K.H.G.M and the SFI Starting Investigator Research Grant 13/SIRG/2130 to A.M.C.

Comments

The original article is available at https://www.nature.com/articles/s41467-017-02111-0

Abstract

The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). In myeloid cells, BMAL1 maintains anti-inflammatory responses and reduces T cell polarization. Loss of myeloid BMAL1 or midday immunizations to induce EAE create an inflammatory environment in the CNS through expansion and infiltration of IL-1β-secreting CD11b+Ly6Chi monocytes, resulting in increased pathogenic IL-17+/IFN-γ+ T cells. These findings demonstrate the importance of the molecular clock in modulating innate and adaptive immune crosstalk under autoimmune conditions.

Disciplines

Life Sciences

Citation

Sutton CE, Finlay CM, Raverdeau M, Early JO, DeCourcey J, Zaslona Z, O'Neill LAJ, Mills KHG, Curtis AM. Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune diseas. Nature Communications. 2017;8(1):1923.

PubMed ID

29234010

DOI Link

10.1038/s41467-017-02111-0

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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