Nicotinamide Riboside Reduces T Cell Exhaustion and Improves Survival in Sepsis: Preclinical Findings

Synopsis

Sepsis, a life-threatening response to infection, often causes the immune system to weaken through T cell exhaustion, leading to poor recovery and high mortality. This study found that in septic mice, NAD+ levels and the activity of SIRT1, a key NAD+-dependent enzyme that supports immune balance, were significantly reduced. Treatment with nicotinamide riboside (NR)—a vitamin B3–derived NAD+ booster—restored both NAD+ and SIRT1 levels. As a result, T cell loss in the spleen was prevented, CD4+ and CD8+ T cell populations recovered, and immune balance between Th1 and Th2 cells was normalized. NR also reduced regulatory T cell expansion and PD-1 expression, markers of immune exhaustion. Beyond immune restoration, NR treatment lowered bacterial load, reduced organ damage, and improved survival in septic mice. These findings suggest that NR supplementation may help rejuvenate immune function and protect organs during sepsis through the NAD+/SIRT1 pathway.

Journal

Shock