Flavin adenine dinucleotide is an endogenous suppressor for cytosolic DNA and RNA sensors to modulate innate immunity.
FAD acts as a natural suppressor of cytosolic DNA and RNA sensors, reducing immune activation and inflammation, with levels dropping during viral infections to enhance immunity.
- Why it matters: Understanding how innate immune responses are regulated is vital for developing therapies for autoinflammatory and infectious diseases, yet endogenous mechanisms remain unclear.
- What they did: Researchers identified FAD as an endogenous metabolite that binds directly to cGAS and RIG-I, inhibiting their activity; they studied FAD levels and immune responses in cells and mice, including FAD synthase (FLAD1) knockout models.
- The result: FAD deficiency led to increased inflammation and cellular aging, while reduced FLAD1 activity during infection boosted immune responses, suggesting FAD modulation could be targeted to treat inflammatory conditions.