"Conventional DCs reduce liver ischemia/reperfusion injury in mice via " by Zubin M Bamboat, Lee Ocuin MD et al.
 

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

Publication/Presentation Date

2-1-2010

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.

Volume

120

Issue

2

First Page

559

Last Page

569

ISSN

1558-8238

Disciplines

Medicine and Health Sciences

PubMedID

20093775

Department(s)

Department of Surgery, Lehigh Valley Topper Cancer Institute

Document Type

Article

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