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Updated: May 10, 2026
Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion
Zubin M Bamboat1, Lee M Ocuin, Vinod P Balachandran
1Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center (MSKCC), New York, New York 10065, USA.
Abstract:
TLRs are recognized as promoters of tissue damage, even in the absence of pathogens. TLR binding to damage-associated molecular patterns (DAMPs) released by injured host cells unleashes an inflammatory cascade that amplifies tissue destruction. However, whether TLRs possess the reciprocal ability to curtail the extent of sterile inflammation is uncertain. Here, we investigated this possibility in mice by studying the role of conventional DCs (cDCs) in liver ischemia/reperfusion (I/R) injury, a model of sterile inflammation. Targeted depletion of mouse cDCs increased liver injury after I/R, as assessed by serum alanine aminotransferase and histologic analysis. In vitro, we identified hepatocyte DNA as an endogenous ligand to TLR9 that promoted cDCs to secrete IL-10. In vivo, cDC production of IL-10 required TLR9 and reduced liver injury. In addition, we found that inflammatory monocytes recruited to the liver via chemokine receptor 2 were downstream targets of cDC IL-10. IL-10 from cDCs reduced production of TNF, IL-6, and ROS by inflammatory monocytes. Our results implicate inflammatory monocytes as mediators of liver I/R injury and reveal that cDCs respond to DAMPS during sterile inflammation, providing the host with protection from progressive tissue damage.
Insights
Conventional dendritic cells (cDCs) protect the liver from sterile inflammation by responding to damage-associated molecular patterns (DAMPs). cDCs secrete IL-10 via TLR9, which suppresses inflammatory monocytes and limits tissue damage in liver ischemia/reperfusion injury.
Area of Science:
- Immunology
- Inflammation Biology
- Hepatology
Background:
- Toll-like receptors (TLRs) are known to exacerbate sterile tissue damage by responding to damage-associated molecular patterns (DAMPs).
- The potential role of TLRs in resolving sterile inflammation remains largely unexplored.
- Liver ischemia/reperfusion (I/R) injury serves as a critical model for studying sterile inflammation.
Purpose of the Study:
- To investigate whether Toll-like receptors (TLRs) can limit sterile inflammation.
- To elucidate the role of conventional dendritic cells (cDCs) in liver ischemia/reperfusion (I/R) injury.
Main Methods:
- Depletion of cDCs in mice subjected to liver I/R injury.
- In vitro assessment of hepatocyte DNA as a ligand for TLR9 on cDCs.
- Measurement of IL-10 secretion by cDCs and its effect on inflammatory monocytes.
Main Results:
- Depletion of cDCs exacerbated liver I/R injury.
- Hepatocyte DNA was identified as a TLR9 ligand that induced IL-10 production in cDCs.
- cDC-derived IL-10, dependent on TLR9, reduced liver injury by suppressing TNF, IL-6, and ROS production in inflammatory monocytes.
Conclusions:
- Conventional dendritic cells (cDCs) play a protective role in sterile liver inflammation.
- cDCs, through TLR9 activation by DAMPs, secrete IL-10 to mitigate liver I/R injury.
- Inflammatory monocytes are key mediators of liver I/R injury, and their inflammatory functions are suppressed by cDC-derived IL-10.
