CX3CR1 modulates the anti-inflammatory activity of hepatic dendritic cells in response to acute liver injury

2017 ◽  
Vol 131 (17) ◽  
pp. 2289-2301 ◽  
Author(s):  
Salvatore Sutti ◽  
Felix Heymann ◽  
Stefania Bruzzì ◽  
Julia Peusquens ◽  
Christian Trautwein ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Liver Injury ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Cell Types ◽  
Interleukin 10 ◽  
Chemokine Ligand ◽  
Anti Inflammatory

The chemokine fractalkine (C–X3–C motif chemokine ligand 1, CX3CL1) and its receptor (C–X3–C motif chemokine receptor 1, CX3CR1) are known to mediate leukocyte chemotaxis, adhesion, and survival. In the liver, CX3CR1 is expressed on multiple cell types including monocytes and dendritic cells. However, the function of CX3CR1 on hepatic dendritic cells (HDCs) is still poorly understood. In the present study, we investigated the role of CX3CR1 on mouse HDCs during homeostasis and following acute liver injury. At homeostasis, CX3CR1 expression was detected amongst CD11b+/CD103− type 2 myeloid HDCs (mHDCs) and these cells were characterized by the production of interleukin-10 (IL-10). Mice treatment with the hepatotoxic agent carbon tetrachloride (CCl4) up-regulated liver IL-10 expression and stimulated the expansion of CX3CR1+ mHDCs which also showed a more mature phenotype. The absence of CX3CR1 in naïve CX3CR1gfp/gfp mice specifically reduced the CD11b+/IL-10+ mHDCs as compared with CX3CR1-proficient animals (CX3CR1+/gfp). Following CCl4 poisoning, the liver recruitment and maturation of CD11b+ mHDCs was significantly attenuated in CX3CR1gfp/gfp mice. Furthermore, these mice suffered more severe hepatic injury and inflammation than CX3CR1+/gfp mice and showed a delated recovery from liver damage. Such a worsening of liver injury in CX3CR1gfp/gfp mice was associated with an impaired up-regulation of hepatic IL-10 expression and a lower number of IL-10 producing CD11b+ mHDCs. Consistently, IL-10 inactivation enhanced hepatic injury and inflammation in CX3CR1+/gfp mice receiving CCl4. Altogether, these data indicate a novel role of the CX3CL1/CX3CR1 axis in liver type 2 mHDC functions, pointing out the importance of CX3CR1 in promoting IL-10-mediated anti-inflammatory actions of HDCs.

scholarly journals The role of non-steroidal anti-inflammatory drugs in acute liver injury.

BMJ ◽  
1992 ◽  
Vol 305 (6858) ◽  
pp. 865-868 ◽  
Author(s):  
L. A. Garcia Rodriguez ◽  
S. Perez Gutthann ◽  
A. M. Walker ◽  
L. Lueck
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals The Role of Non-steroidal Anti-inflammatory Drugs in Acute Liver Injury

1993 ◽  
Vol XXXVII (3) ◽  
pp. 139
Author(s):  
LUIS A. GARCIA RODRIGUEZ ◽  
SUSANNE PEREZ GUTTHANN ◽  
ALEXANDER M. WALKER ◽  
LEAH LUECK
Keyword(s):  
Liver Injury ◽  
Acute Liver Injury ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells

2009 ◽  
Vol 206 (9) ◽  
pp. 1863-1871 ◽  
Author(s):  
Frank Kaiser ◽  
Dorthe Cook ◽  
Stamatia Papoutsopoulou ◽  
Ricardo Rajsbaum ◽  
Xuemei Wu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cell Types ◽  
Interleukin 10 ◽  
Interferon Β ◽  
Myeloid Dendritic Cells ◽  
Retroviral Transduction ◽  
Erk Activation ◽  
Extracellular Signal ◽  
Factor C

Stimulation of Toll-like receptors (TLRs) on macrophages and dendritic cells (DCs) by pathogen-derived products induces the production of cytokines, which play an important role in immune responses. Here, we investigated the role of the TPL-2 signaling pathway in TLR induction of interferon-β (IFN-β) and interleukin-10 (IL-10) in these cell types. It has previously been suggested that IFN-β and IL-10 are coordinately regulated after TLR stimulation. However, in the absence of TPL-2 signaling, lipopolysaccharide (TLR4) and CpG (TLR9) stimulation resulted in increased production of IFN-β while decreasing IL-10 production by both macrophages and myeloid DCs. In contrast, CpG induction of both IFN-α and IFN-β by plasmacytoid DCs was decreased in the absence of TPL-2, although extracellular signal-regulated kinase (ERK) activation was blocked. Extracellular signal-related kinase–dependent negative regulation of IFN-β in macrophages was IL-10–independent, required protein synthesis, and was recapitulated in TPL-2–deficient myeloid DCs by retroviral transduction of the ERK-dependent transcription factor c-fos.

The paracaspase MALT1 in psoriasis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Stephan Hailfinger ◽  
Klaus Schulze-Osthoff
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factors ◽  
Skin Disease ◽  
Cell Types ◽  
Cytokine Receptors ◽  
Molecular Scaffold ◽  
Therapeutic Implications ◽  
Stimulation Of

Abstract Psoriasis is a frequent autoimmune-related skin disease, which involves various cell types such as T cells, keratinocytes and dendritic cells. Genetic variations, such as mutations of CARD14, can promote the development of the disease. CARD14 mutations as well as the stimulation of immune and cytokine receptors activate the paracaspase MALT1, a potent activator of the transcription factors NF-κB and AP-1. The disease-promoting role of MALT1 for psoriasis is mediated by both its protease activity as well as its molecular scaffold function. Here, we review the importance of MALT1-mediated signaling and its therapeutic implications in psoriasis.

scholarly journals Acute liver injury associated with Oxyfluorfen toxicity

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110004
Author(s):  
Selladurai Pirasath ◽  
Ayshanie Gayanthika Samasundara Mudiyanselage ◽  
Manosha Harshani Seneviratne
Keyword(s):  
Sri Lanka ◽  
Liver Injury ◽  
Young Woman ◽  
Broad Spectrum ◽  
Hepatic Injury ◽  
Acute Liver Injury ◽  
Toxic Dose ◽  
Acute Hepatic Injury ◽  
Haem Biosynthesis ◽  
Spectrum Control

Oxyfluorfen is a phenoxyphenyl-type herbicide which is used for broad-spectrum control of broadleaf and grassy weeds. Ingestion of toxic dose of oxyfluorfen can be fatal among animals. However, toxicity to humans are rare in literature. The alterations in haem biosynthesis (anaemia) and in liver are the primary toxic effects. There are no specific antidotes and none of the current treatments have proven efficacious till date. Therefore, prevention needs to be the utmost priority, and on exposure, aggressive decontamination should be initiated. Herein, we described an oxyfluorfen toxicity with acute hepatic injury in a young woman who presented with a deliberate self-harming with an oxyfluorfen poisoning in Sri Lanka.

scholarly journals Dual Role of Interleukin-10 in Murine NZB/W F1 Lupus

2021 ◽  
Vol 22 (3) ◽  
pp. 1347
Author(s):  
Anaïs Amend ◽  
Natalie Wickli ◽  
Anna-Lena Schäfer ◽  
Dalina T. L. Sprenger ◽  
Rudolf A. Manz ◽  
...  
Keyword(s):  
B Cell ◽  
Disease Model ◽  
Interleukin 10 ◽  
Immune Functions ◽  
Murine Lupus ◽  
Anti Inflammatory ◽  
In Vivo Effects

As a key anti-inflammatory cytokine, IL-10 is crucial in preventing inflammatory and autoimmune diseases. However, in human and murine lupus, its role remains controversial. Our aim was to understand regulation and immunologic effects of IL-10 on different immune functions in the setting of lupus. This was explored in lupus-prone NZB/W F1 mice in vitro and vivo to understand IL-10 effects on individual immune cells as well as in the complex in vivo setting. We found pleiotropic IL-10 expression that largely increased with progressing lupus, while IL-10 receptor (IL-10R) levels remained relatively stable. In vitro experiments revealed pro- and anti-inflammatory IL-10 effects. Particularly, IL-10 decreased pro-inflammatory cytokines and slowed B cell proliferation, thereby triggering plasma cell differentiation. The frequent co-expression of ICOS, IL-21 and cMAF suggests that IL-10-producing CD4 T cells are important B cell helpers in this context. In vitro and in vivo effects of IL-10 were not fully concordant. In vivo IL-10R blockade slightly accelerated clinical lupus manifestations and immune dysregulation. Altogether, our side-by-side in vitro and in vivo comparison of the influence of IL-10 on different aspects of immunity shows that IL-10 has dual effects. Our results further reveal that the overall outcome may depend on the interplay of different factors such as target cell, inflammatory and stimulatory microenvironment, disease model and state. A comprehensive understanding of such influences is important to exploit IL-10 as a therapeutic target.

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