NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation

NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated with inflammatory and infectious diseases, but little is known about its function as an innate immune sensor and cell death regulator. Therefore, we screened for NLRC5’s role in response to infections, PAMPs, DAMPs, and cytokines. We identified that NLRC5 acts as an innate immune sensor to drive inflammatory cell death, PANoptosis, in response to specific ligands, including PAMP/heme and heme/cytokine combinations. NLRC5 interacted with NLRP12 and PANoptosome components to form a cell death…

• AL
  American Lebanese Syrian Associated Charities

  Awards: AI124346, AR056296, AI101935
• NI
  National Institutes of Health

  Awards: AR056296, CA253095, AI101935, AI124346, AI160179
• G
  Genentech

  Awards: WO 2024/097571 A1, 63/501,430