The Journal of experimental medicineDec 12, 2025

How Body Clocks Help Control Inflammation by Guiding Neutrophils

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

A CXCL12-CXCR4 circadian checkpoint can reposition neutrophils and reduce inflammatory tissue injury in experimental models.

Evidence

The study reports mechanistic preclinical experiments linking diurnal CXCL12 peaks, neutrophil clock inhibition, CXCR4 signaling, genetic manipulation, and synthetic CXCR4 agonist treatment to myocardial and vascular injury outcomes.

Caveat

The abstract describes experimental injury protection and tissue mechanisms, not human clinical efficacy or long-term safety of activating this pathway.

Simplified

Inflammation-driven injury, a significant source of morbidity and mortality worldwide, is largely mediated by the cytotoxic activities of neutrophils, which extend the initial lesion and jeopardize organ function. Intriguingly, inflammatory injury naturally declines at specific times of day, suggesting that circadian mechanisms exist that mitigate the destructive activity of neutrophils and protect the host. Here, we show that the periods of diurnal protection coincide with peaks in plasma CXCL12, a chemokine that inhibits the neutrophil-intrinsic circadian clock by signaling through CXCR4. Genetic deletion of this clock, or a hyperactive form of CXCR4, prevented the diurnal spikes of injury, and treatment with a synthetic CXCR4 agonist conferred protection from myocardial and vascular injury. In tissues, this protection was mediated by repositioning neutrophils in the wound core, which spared neighboring host cells from apoptotic death. Thus, a circadian neutrophil checkpoint protects from exuberant inflammation and can be activated to protect the host.