Longevity & AgingExhausted Immune Cells Spread Dysfunction Like Infection — and a Key Enzyme Stops It
Monocyte exhaustion — a dysfunctional immune state seen in sepsis and chronic inflammation — can spread from depleted cells to healthy neighboring monocytes through direct cell-to-cell contact, not just soluble signals. Researchers identified CD38, a metabolic enzyme that depletes the vital cofactor NAD⁺, and mTOR signaling as central regulators of this propagation. Exhausted monocytes also damaged blood vessel lining cells, boosted inflammatory adhesion molecules, and suppressed T cell activity. Crucially, blocking CD38 with the inhibitor 78c or inhibiting mTOR partially reversed these harmful effects, restoring monocyte function and protecting endothelial and T cell health. These findings point to the CD38–mTOR axis as a promising therapeutic target in inflammatory and immune-exhaustion diseases.
