The fate of dendritic cells in a mouse model of liver ischemia/reperfusion injury

Loi, Patrizia; Paulart, Frédéric; Pajak, Bernard; Nagy, Nathalie; Salmon, Isabelle; Moser, Muriel; Goldman, Michel; Flamand, Véronique

doi:10.1016/j.transproceed.2004.05.052

Cited by 28 publications

(23 citation statements)

References 21 publications

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“…We noted a time-dependent increase in liver cDC death that peaked at 12 hours after initiation of ischemia ( Figure 1C). In line with earlier work by Loi et al (16), we found that the remaining cDCs within the ischemic lobes were mature, with increased expression of CD40, CD80, and CD86 ( Figure 1D). Similar maturation of cDCs occurred in the segments of the liver that were not subjected to ischemia (data not shown).…”

Section: Introductionsupporting

confidence: 92%

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

Bamboat¹,

Ocuin²,

et al. 2010

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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.

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Section: Introductionsupporting

confidence: 92%

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

Bamboat¹,

Ocuin²,

et al. 2010

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“…Original magnification was ϫ50. other studies have demonstrated that dendritic cells are activated by Toll-like receptor-mediated pathway and increase their expression of MHC class II during hepatic I/R injury, leading to antigen-dependent activation of CD4 ϩ T cells (30,40). Moreover, blockade of TCR signaling with cyclosporine treatment is known to reduce hepatic I/R injury (24,35).…”

Section: Discussionmentioning

confidence: 99%

Distinct contributions of CD4⁺T cell subsets in hepatic ischemia/reperfusion injury

Kuboki¹,

Sakai²,

Tschöp³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…DCs, the most potent APCs, play an important role in the pathogenesis of hepatic IRI (35,37). The potential mechanisms of DCs' insult on the liver are that they migrate into the injured sinusoids, subsequently activate CD4 ϩ T cells and allow them to release proinflammatory cytokines, which initiate and maintain the local inflammatory response and tissue injury accompanied with PMN and macrophage infiltration.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Rat Leukocyte P-Selectin Glycoprotein Ligand-1 and Effect of Its Blockade: Protection from Ischemia-Reperfusion Injury in Liver Transplantation

Tsuchihashi

Fondevila

Shaw³

et al. 2006

The Journal of Immunology

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P-selectin glycoprotein ligand-1 (PSGL-1) mediates the initial tethering of leukocytes to activated platelets and endothelium. We report molecular cloning and characterization of the rat PSGL-1 gene. A neutralizing Ab was generated, and its binding epitope was mapped to the N-terminal binding region of rat PSGL-1. We examined the effects of early PSGL-1 blockade in rat liver models of cold ischemia, followed by ex vivo reperfusion or transplantation (orthotopic liver transplantation (OLT)) using an anti-PSGL-1 Ab with diminished Fc-mediated effector function. In the ex vivo hepatic cold ischemia and reperfusion model, pretreatment with anti-PSGL-1 Ab improved portal venous flow, increased bile production, and decreased hepatocellular damage. Rat pretreatment with anti-PSGL-1 Ab prevented hepatic insult in a model of cold ischemia, followed by OLT, as assessed by 1) decreased hepatocellular damage (serum glutamic oxaloacetic transaminase/glutamic-pyruvic transaminase levels), and ameliorated histological features of ischemia/reperfusion injury, consistent with extended OLT survival; 2) reduced intrahepatic leukocyte infiltration, as evidenced by decreased expression of P-selectin, ED-1, CD3, and OX-62 cells; 3) inhibited expression of proinflammatory cytokine genes (TNF-α, IL-1β, IL-6, IFN-γ, and IL-2); and 4) prevented hepatic apoptosis accompanied by up-regulation of antiapoptotic Bcl-2/Bcl-xL protective genes. Thus, targeting PSGL-1 with a blocking Ab that has diminished Fc-mediated effector function is a simple and effective strategy that provides the rationale for novel therapeutic approaches to maximize the organ donor pool through the safer use of liver transplants despite prolonged periods of cold ischemia.

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The fate of dendritic cells in a mouse model of liver ischemia/reperfusion injury

Cited by 28 publications

References 21 publications

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

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

Distinct contributions of CD4⁺T cell subsets in hepatic ischemia/reperfusion injury

Molecular Characterization of Rat Leukocyte P-Selectin Glycoprotein Ligand-1 and Effect of Its Blockade: Protection from Ischemia-Reperfusion Injury in Liver Transplantation

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The fate of dendritic cells in a mouse model of liver ischemia/reperfusion injury

Cited by 28 publications

References 21 publications

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

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

Distinct contributions of CD4+T cell subsets in hepatic ischemia/reperfusion injury

Molecular Characterization of Rat Leukocyte P-Selectin Glycoprotein Ligand-1 and Effect of Its Blockade: Protection from Ischemia-Reperfusion Injury in Liver Transplantation

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Distinct contributions of CD4⁺T cell subsets in hepatic ischemia/reperfusion injury