Macrophage metabolic exhaustion and PANoptotic cell death drive chronic tissue inflammation in rheumatoid arthritis - PubMed
5 days ago
- #macrophage metabolism
- #PANoptosis
- #rheumatoid arthritis
- Macrophage metabolic exhaustion and PANoptotic cell death contribute to chronic inflammation in rheumatoid arthritis.
- Synovial SELENOPhiMerTK+CD206+ macrophages in patients produce high levels of C1q and express its receptor C1QBP.
- C1q stimulation leads to metabolic exhaustion in macrophages, reducing ATP production and increasing cADPR accumulation.
- The mitochondrial enzyme SARM1 drives this metabolic crisis by converting NAD into cADPR, triggering PANoptotic death.
- In vivo, C1q worsens synovitis, while SARM1 inhibition provides therapeutic benefits.
- SARM1 is identified as a marker of metabolically stressed macrophages and a driver of pro-inflammatory death in autoimmune inflammation.