Taurine leaves macrophages before the NLRP3 inflammatory complex assembles
Taurine leaves macrophages before the NLRP3 inflammatory complex assembles
On October 23, Cell published a paper by Chenyang Guan and colleagues: in macrophage experiments, several danger signals caused taurine to leave the cells, while adding taurine suppressed NLRP3 assembly. In twenty-month-old mice, four months of taurine in drinking water reduced levels of several inflammatory proteins and improved grip strength, coordination, and glucose regulation. In participants in the CALERIE-II calorie restriction study, taurine and hypotaurine levels in subcutaneous fat increased after a year of moderate calorie restriction.
In a 2023 Science paper, blood taurine levels declined with age in mice, monkeys, and humans, and taurine supplementation extended lifespan in mice. In new human and mouse cohorts, Guan and colleagues found the opposite pattern: taurine levels increased with age. The researchers then examined taurine inside macrophages as the cells received a danger signal.
Macrophages are immune cells that respond to tissue damage. They can assemble the NLRP3 inflammasome, a protein complex that activates the enzyme caspase-1. This enzyme helps the cell release IL-1β and IL-18, proteins that signal inflammation. Senior author Vishwa Deep Dixit described the starting question in a Yale School of Medicine news release:
“The innate immune system does not have a separate receptor for every type of danger signal, so how it recognizes these signals has remained a puzzle.”
The researchers tested several NLRP3 activators: ATP, which cells release when damaged; urate crystals; and a more dilute culture medium. Each caused taurine to leave macrophages. The cells then lost potassium, assembled the NLRP3 inflammasome, activated caspase-1, and released IL-1β and IL-18. Adding taurine reduced potassium loss and assembly of the complex.
Neither an NLRP3 blocker nor a solution with a high potassium concentration stopped taurine release. The researchers therefore placed taurine release before potassium loss and complex assembly in the sequence of events. In experiments involving two other inflammatory complexes, AIM2 and NLRC4, added taurine left the response unchanged. This links the effect specifically to NLRP3.
Twenty-month-old mice received taurine in their drinking water for four months. Their IL-1β, IL-18, and IL-6 levels fell, while grip strength, coordination, and glucose regulation improved. In CALERIE-II participants, taurine and hypotaurine levels in subcutaneous fat increased after a year of moderate calorie restriction, while several inflammasome-related genes became less active. In a previous CALERIE analysis, calorie restriction also coincided with a decline in C3a, a signaling molecule from another branch of innate immunity.
In the cell experiments, different danger signals led to the same sequence of events: taurine first left the macrophage, after which the cell lost potassium and assembled the NLRP3 inflammasome.