The neuroscience of circadian rhythms -- the internal 24-hour clocks that control almost every physiological function in our bodies -- was the subject of one of the most interesting lectures we attended this semester. Although many individuals associate the circadian clock with the sleep-wake cycle, this clock, which is controlled by the brain's master pacemaker in the suprachiasmatic nucleus (SCN), is a systemic regulator that controls hormone release, metabolism, and even susceptibility to illness. The lesson was that the timing of a bodily event -- such as a meal, a medication dosage, or the start of an infection -- is frequently just as significant as the event itself. A recent study linking the body internal clock to the fight against inflammation immediately resonated with this notion of biological timing as a crucial component of systemic health. "Targeting Nuclear Receptors for TH17-Mediated Inflammation: REV-ERBations of Circadian Rhythm and Metabolism," a mini-review by Mosure, Wilson, and Solt (2022), emphasizes a clear connection between the immune system and the time-keeping system.
The study focuses on T helper 17 cells, and immune cell type that is essential for both warding off external pathogens and, when overactivated, causing autoimmune diseases like inflammatory bowel disease, psoriasis, and multiple sclerosis. This work highlights the importance of a cells internal and external factors, particularly metabolism, in determining TH17 cells are pathogenic (harmful) or non-pathogenic (helpful), independent of classical signaling pathways.
REV-ERB, a nuclear receptor protein, is the crucial component. According to the review, REV-ERB functions as a central hub that connects the body's general circadian rhythm to the particular metabolic state of TH17 cells and is a component of the core molecular clock mechanism. Essentially, these immune cells' pro-inflammatory activity is influenced by the central clock, which uses REV-ERB to control when and how these cells fuel themselves. The authors propose that targeting REV-ERB has potential for treatment for TH17-mediated autoimmune disorders because it serves as a link between immune function and the circadian clock.
The relationship between this article and our discussion in class changes how we should understand news about autoimmune and inflammatory diseases along with circadian rhythms. Although environmental pollutants, genetics, and diet are frequently blamed in headlines, this study adds a significant temporal element. Chronotherapy is the idea of manipulating our eating, sleeping, or anti-inflammatory medication schedules to improve therapeutic results if the degree of inflammation is correlated with the rhythmic activity of immune cells.
The talk centered on the master clock. But other research points out the intricate working of these systems. Take a 20205 study from Guerrero and colleagues. They looked at fruit fly models, or Drosophila. It turns out the single molecular clock is not really needed for those Lateral Posterior Clock Neurons, the LPNs, to control rest-activity patterns. What matters more is the signaling from these LPSs to targets further down the line. That keeps the rhythms going strong. This result really drives home how layered and detailed the brain's clock setup is. It depends on molecular timing plus all that back-and-forth between neurons.
These studies show us that the brains circadian system, does not work like some basic daily timer. It acts more as a central director managing a really intricate range of body processes. That covers thing like a tight metabolic timing for the immune system. Grasping this stronger connection among brain science, metabolism, and immune responses matters a lot. It helps explain major illnesses and could lead to better ways of treating them in real life.
Guerrero, C. Y. P., Cusick, M. R., Samaras, A. J., Shamon, N. S., & Cavanaugh, D. J. (2025). The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation of Drosophila rest-activity rhythms. Neurobiology of sleep and circadian rhythms, 18, 100124. https://doi.org/10.1016/j.nbscr.2025.100124
Mosure, S. A., Wilson, A. N., & Solt, L. A. (2022). Targeting Nuclear Receptors for TH17-Mediated Inflammation: REV-ERBerations of Circadian Rhythm and Metabolism. Immunometabolism (Cobham), 4(2). https://doi.org/10.20900/immunometab20220006
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