Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion Journal Article
| Authors: | Bamboat, Z. M.; Ocuin, L. M.; Balachandran, V. P.; Obaid, H.; Plitas, G.; DeMatteo, R. P. |
| Article Title: | Conventional DCs reduce liver ischemia/reperfusion injury in mice via IL-10 secretion |
| 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. |
| Keywords: | controlled study; nonhuman; flow cytometry; animal cell; mouse; animals; mice; hepatocytes; dendritic cell; interleukin 10; animal experiment; animal model; inflammation; in vivo study; in vitro study; histology; alanine aminotransferase blood level; molecular mechanics; alanine aminotransferase; dendritic cells; dna; ligand; interleukin 6; reactive oxygen metabolite; liver cell; monocyte; monocytes; cytokine release; tissue injury; chemokine receptor ccr2; receptors, ccr2; liver injury; depletion; tumor necrosis factor; host; interleukin-10; toll-like receptor 9; toll like receptor 9; reperfusion injury; cell dna; liver ischemia; liver protection; mediator; antigens, cd40; antigens, cd80; antigens, cd86 |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 120 |
| Issue: | 2 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2010-02-01 |
| Start Page: | 559 |
| End Page: | 569 |
| Language: | English |
| DOI: | 10.1172/jci40008 |
| PUBMED: | 20093775 |
| PROVIDER: | scopus |
| PMCID: | PMC2810082 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 10" - "Export Date: 20 April 2011" - "CODEN: JCINA" - "Source: Scopus" |
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