Metabolic licensing of innate immune memory.

NAD+ is revealed as a metabolic signal that preserves an epigenetic mark central to trained immunity by inhibiting the histone demethylase KDM5a.

• Why it matters: Trained immunity depends on maintaining specific epigenetic states, but how metabolic cues sustain these marks is not fully defined.
• What they did: The work identifies NAD+ as a metabolic signal and links its effect to inhibition of the histone demethylase KDM5a, preserving a key epigenetic mark.
• The result: By showing NAD+ can preserve this epigenetic feature through KDM5a inhibition, the study supports a metabolic licensing mechanism for innate immune memory.

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