Overview
- UCLA researchers report in the Journal of Experimental Medicine that macrophage memory relies on ongoing low-level interferon gamma signaling.
- A brief IFNγ exposure generated thousands of enhancer domains that persisted for days and heightened responses to bacterial molecules.
- Small amounts of IFNγ remained associated with macrophages and nearby tissue, and this residual signaling proved necessary to maintain the potentiated state.
- Neutralizing IFNγ or blocking JAK signaling erased the enhancers and dampened macrophage responses, demonstrating pharmacological reversibility.
- The authors note consistency with mouse studies reversing BCG-trained immunity and suggest therapeutic potential for autoimmune diseases, while stressing unanswered questions about other stimuli and in vivo relevance.