Abstract
The circadian clock orchestrates daily rhythms in many physiological, behavioral and molecular processes, providing means to anticipate, and adapt to environmental changes. A specific role of the circadian clock is to coordinate functions of the immune system both at steady-state and in response to infectious threats. Hence, time-of-day dependent variables are found in the physiology of immune cells, host-parasite interactions, inflammatory processes, or adaptive immune responses. Interestingly, the molecular clock coordinates transcriptional-translational feedback loops which orchestrate daily oscillations in expression of many genes involved in cellular functions. This clock function is assisted by tightly controlled transitions in the chromatin fiber involving epigenetic mechanisms which determine how a when transcriptional oscillations occur. Immune cells are no exception, as they also present a functional clock dictating transcriptional rhythms. Hereby, the molecular clock and the chromatin regulators controlling rhythmicity represent a unique scaffold mediating the crosstalk between the circadian and the immune systems. Certain epigenetic regulators are shared between both systems and uncovering them and characterizing their dynamics can provide clues to design effective chronotherapeutic strategies for modulation of the immune system.
Highlights
The immune response is perhaps the most evident organismal response against infection, and mounting research depicts the circadian system as a critical regulator of immune defense
Acute inflammation induces a genome wide re-localization of CLOCK:BMAL1 to sites in proximity to genes involved in the immune system response or interferon signaling, most of them bound by p65 and with increased H3K27ac and polymerase II (Hong et al, 2018)
Chronic inflammatory responses such as those associated with unbalanced diets are accompanied by a re-localization of p65 to core clock repressor genes, including Per1 and Rev-erbα, which in turn decrease their transcription, while CLOCK:BMAL1 complexes become active at sites associated with the immune response in the mouse liver (Hong et al, 2018)
Summary
The immune response is perhaps the most evident organismal response against infection, and mounting research depicts the circadian system as a critical regulator of immune defense. When cultured mouse bone marrow-derived macrophages (BMDMs) are activated through the TLR4 receptor, Bmal1 deletion profoundly alters the NF-κB signaling pathway, and extends the inflammatory response trough overexpression of proinflammatory genes (Oishi et al, 2017).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
