summary: New research reveals how the body’s circadian clock regulates macrophage activity and influences immune system inflammation throughout the day. Activation of the NLRP3 inflammasome, a key component of the immune response, peaks in the morning when macrophages are most efficient. This daily rhythm is driven by mitochondrial activity, which explains why inflammatory conditions such as arthritis are often worse in the morning.
This discovery opens the door to time-targeted therapies and could improve treatments for diseases caused by excess inflammasomes. Understanding the immune system’s biological clock can lead to precise interventions against inflammatory diseases.
Important facts:
- Daily immune rhythm: The circadian clock regulates macrophage inflammasome activation, which peaks in the morning.
- Role of mitochondria: Mitochondria drive time-dependent changes in immune responses.
- Treatment possibilities: Adjusting the timing of treatment to the immune activity cycle may improve the management of inflammatory diseases.
sauce: RCSI
New research from the RCSI School of Medicine and Health Sciences has explained how the body clock influences the immune system’s inflammatory processes.
The findings explain how immune cells called macrophages work differently at different times of the day, potentially paving the way for time-targeted treatments for inflammatory diseases such as arthritis. There is.
Researchers investigated the connection between the immune system and the body’s circadian rhythm, often referred to as the body clock. Macrophages are immune cells that detect and respond to harmful substances and can trigger inflammation as a defense mechanism by assembling large complexes known as inflammasomes.
Inflammasomes can be compared to “smoke alarms” that alert the immune system to danger.
Activation of an inflammasome called NLRP3 was found not to be constant throughout the day, but is regulated by the body’s 24-hour circadian clock. This daily rhythm determines when macrophages are most efficient at detecting threats and when their energy levels are at their peak to mount a response.
The study also highlights the critical role of mitochondria, the cells’ energy producers, in driving daily changes in immune activity.
“When macrophages ‘think’ it’s morning, their inflammasome activation becomes faster and more powerful,” explains Professor Annie Curtis, lead researcher at RCSI’s School of Pharmaceutical and Biomolecular Sciences.
“This means that our immune response is heightened earlier in the day, when we are awake, and we are more likely to encounter environmental challenges such as injury or infection.”
This study has important implications for the understanding and treatment of inflammatory diseases such as arthritis, where overactive inflammasomes play an important role. Symptoms of such illnesses are often worse in the morning, and this study may help explain it.
“These findings have the potential to improve treatments for inflammatory conditions,” said Dr. James Osiolein, lead author of the study.
“For example, new treatments that target inflammasomes may be more effective if administered during specific times of day when macrophage activity is at its peak.”
Funding: This research was supported by funding from Taighde Éireann of Research Ireland.
About this circadian rhythm and inflammation research news
author: laura anderson
sauce: RCSI
contact: Laura Anderson – RCSI
image: Image credited to Neuroscience News
Original research: Open access.
“Mitochondrial time control regulates NLRP3 inflammasome activation in macrophagesWritten by Annie Curtis et al. FASEB Journal
abstract
Mitochondrial time control regulates NLRP3 inflammasome activation in macrophages
Macrophages are innate immune cells that coordinate time-of-day processes of inflammation. This ensures proper biological timing of the immune response to the external environment.
The NLRP3 inflammasome mediates IL-1 family cytokine release via pyroptosis. Mitochondria play multifaceted roles in regulating NLRP3 inflammasome activity.
Mitochondria exhibit distinct metabolic changes depending on the time of day, which is influenced by clock genes. However, whether the macrophage clock regulates the NLRP3 inflammasome through mitochondrial control remains unknown.
Increased mitochondrial membrane potential (Δψm) and enhanced NLRP3 inflammasome activation from peritoneal exudate cells (PECs) isolated at circadian time (CT) 12 compared to circadian time (CT) 0 You can see it.
In vitro time synchronization of bone marrow-derived macrophages (BMDMs) induced time-dependent differences in NLRP3 inflammasome activation.
bone marrow specific Bmal1-Deletion enhanced NLRP3 inflammasome activity in CT0 PECs and asynchronous BMDMs compared to controls.
Pharmacological disruption of Δψm in synchronous cells reduced NLRP3 inflammasome activation to comparable levels, and the same occurred in cells. Bmal1-delete.
These results further demonstrate that the circadian clock timing of the NLRP3 inflammasome is dependent on mitochondrial function and driven by circadian genes. Bmal1.
