CX3CR1-expressing inflammatory dendritic cells contribute to the progression of steatohepatitis
| Autor: | Cristina Bozzola, Salvatore Sutti, Aastha Jindal, S. Bruzzì, Irene Locatelli, Emanuele Albano, Marco Vacchiano |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
CX3C Chemokine Receptor 1
Gene Expression CD11c Inflammation Sulfides Biology Monocytes Transforming Growth Factor beta1 Methionine Non-alcoholic Fatty Liver Disease medicine Animals Antigens Ly Macrophage CD11b Antigen Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Monocyte Dendritic Cells General Medicine Dendritic cell Flow Cytometry medicine.disease Antigens Differentiation Immunohistochemistry Actins Choline Deficiency Diet Mice Inbred C57BL medicine.anatomical_structure Liver Monocyte differentiation Immunology Disease Progression Receptors Chemokine Tumor necrosis factor alpha medicine.symptom Steatohepatitis |
| Zdroj: | Clinical Science. 129:797-808 |
| ISSN: | 1470-8736 0143-5221 |
| DOI: | 10.1042/cs20150053 |
| Popis: | Liver monocytes play a major role in the development of NASH (non-alcoholic steatohepatitis). In inflamed tissues, monocytes can differentiate in both macrophages and dendritic cells. In the present study, we investigated the role of moDCs (monocyte-derived inflammatory dendritic cells) in experimental steatohepatitis induced in C57BL/6 mice by feeding on a MCD (methionine/choline-deficient) diet. The evolution of steatohepatitis was characterized by an increase in hepatic CD45+/CD11b+ myeloid cells displaying the monocyte/macrophage marker F4-80+. In the early phases (4 weeks of treatment), Ly6Chigh/CD11b+/F4-80+ inflammatory macrophages predominated. However, their frequency did not grow further with the disease progression (8 weeks of treatment), when a 4-fold expansion of CD11b+/F4-80+ cells featuring the fractalkine receptor (CX3CR1) was evident. These CX3CR1+ cells were also characterized by the combined expression of inflammatory monocyte (Ly6C, CD11b) and dendritic cell (CD11c, MHCII) markers as well as by a sustained TNFα (tumour necrosis factor α) production, suggesting monocyte differentiation into inflammatory moDCs. The expansion of TNFα-producing CX3CR1+ moDCs was associated with an elevation in hepatic and circulating TNFα level and with the worsening of parenchymal injury. Hydrogen sulfide (H2S) has been shown to interfere with CX3CR1 up-regulation in monocyte-derived cells exposed to pro-inflammatory stimuli. Treating 4-week-MCD-fed mice with the H2S donor NaHS while continuing on the same diet prevented the accumulation of TNFα-producing CX3CR1+ moDCs without interfering with hepatic macrophage functions. Furthermore, NaHS reduced hepatic and circulating TNFα levels and ameliorated transaminase release and parenchymal injury. Altogether, these results show that inflammatory CX3CR1+ moDCs contributed in sustaining inflammation and liver injury during steatohepatitis progression. |
| Databáze: | OpenAIRE |
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