Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion. Academic Article uri icon

Overview

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.

publication date

  • January 19, 2010

Research

keywords

  • Dendritic Cells
  • Interleukin-10
  • Reperfusion Injury

Identity

PubMed Central ID

  • PMC2810082

Scopus Document Identifier

  • 76649117721

Digital Object Identifier (DOI)

  • 10.1084/jem.20042614

PubMed ID

  • 20093775

Additional Document Info

volume

  • 120

issue

  • 2