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Updated: Jan 31, 2026

Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury
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NLRP3/Caspase-1 Regulate Macrophage Efferocytosis by Modulating ADAM17-Mediated MerTK Cleavage in Liver

Ge Guan1, Chaoqun Yu2,3, Longyu Miao3

  • 1Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Research (Washington, D.C.)
|January 30, 2026
PubMed

Insights

NLRP3/Caspase-1 signaling impairs macrophage efferocytosis in liver ischemia-reperfusion injury (LIRI). Inhibiting ADAM17 restores efferocytosis, reduces LIRI severity, and may offer therapeutic benefits.

Area of Science:

  • Immunology
  • Hepatology
  • Molecular Biology

Background:

  • Macrophage efferocytosis is vital for resolving inflammation in liver ischemia-reperfusion injury (LIRI).
  • The NLRP3/Caspase-1 inflammasome pathway's role in LIRI-associated efferocytosis requires elucidation.

Purpose of the Study:

  • To investigate the impact of NLRP3/Caspase-1 signaling on macrophage efferocytosis during LIRI.
  • To identify the molecular mechanisms linking NLRP3/Caspase-1 activation to efferocytosis dysfunction.
  • To explore potential therapeutic targets for LIRI.

Main Methods:

  • Utilized genetic knockout mouse models (Nlrp3, Caspase-1) and myeloid/hepatocyte-specific knockouts.
  • Assessed LIRI severity, macrophage efferocytosis, and NLRP3/Caspase-1 pathway activation.
  • Investigated ADAM17-mediated MerTK cleavage and its effect on efferocytosis.
  • Analyzed serum soluble MerTK (s-Mer) levels in patients.

Main Results:

  • NLRP3/Caspase-1 pathway is activated early in LIRI, exacerbating injury.
  • Genetic or myeloid-specific deletion of Nlrp3/Caspase-1 reduced LIRI severity.
  • NLRP3/Caspase-1 activation promotes ADAM17-mediated MerTK cleavage, impairing efferocytosis.
  • ADAM17 inhibition restored efferocytosis and alleviated LIRI.
  • Elevated s-Mer levels correlated with LIRI severity and Caspase-1 activation in patients.

Conclusions:

  • NLRP3/Caspase-1 signaling drives LIRI by inhibiting macrophage efferocytosis via ADAM17/MerTK axis.
  • Targeting ADAM17 presents a promising therapeutic strategy for LIRI.
  • Soluble MerTK serves as a potential clinical biomarker for LIRI severity.

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