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Cited by 34Liver physiology and pathologyChemokine receptors and signalingImmune Response and Inflammation

CX3CR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation

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Sutti, Salvatore, Bruzzì, Stefania, Heymann, Felix, Liepelt, Anke, Krenkel, Oliver, Toscani, Alberto, Ramavath, Naresh, Cotella, Diego +2 more·2019·Cells
DOI 10.3390/cells8091099PMC PMC6770190
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Abstract

Recent evidence suggests that hepatic dendritic cells (HDCs) contribute to the evolution of chronic liver diseases. However, the HDC subsets involved and the mechanisms driving these responses are still poorly understood. In this study, we have investigated the role of the fractalkine receptor CX3CR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation. The phenotype of HDC and functional relevance of CX3CR1 was assessed in mice following necro-inflammatory liver injury induced by the hepatotoxic agent carbon tetrachloride (CCl4) and in steatohepatitis caused by a methionine/choline-deficient (MCD) diet. In both the experimental models, hepatic inflammation was associated with a massive expansion of CD11c+/MHCIIhigh/CD11b+ myeloid HDCs. These cells also expressed the monocyte markers Ly6C, chemokine (C-C Motif) receptor 2 (CCR2), F4/80 and CD88, along with CX3CR1, allowing their tentative identification as moDCs. Mice defective in CX3CR1 showed a reduction in liver-moDC recruitment following CCl4 poisoning in parallel with a defective maturation of monocytes into moDCs. The lack of CX3CR1 also affected moDC differentiation from bone marrow myeloid cells induced by granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) in vitro. In wild-type mice, treatment with the CX3CR1 antagonist CX3-AT (150 µg, i.p.) 24 h after CCl4 administration reduced liver moDCS and significantly ameliorated hepatic injury and inflammation. Altogether, these results highlight the possible involvement of moDCs in promoting hepatic inflammation following liver injury and indicated a novel role of CX3CL1/CX3CR1 dyad in driving the differentiation of hepatic moDCs.

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  • IL10 produced by KCs is essential for the liver's physiological role in maintaining immunological tolerance to self-antigens.

    “This phenomenon is very closely related to the functional impairment of liver-resident myeloid cell subsets described above, with IL10 produced by KCs essential for the liver's physiological role in maintaining immunological tolerance to self-antigens (63).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [63]

    The Introduction and Discussion state that IL-10 produced by hepatic dendritic cells contributes to the liver’s tolerogenic environment. They do not identify Kupffer cells as the IL-10 source or establish that their IL-10 is essential for tolerance to self-antigens. (LLM, conf=0.86)

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Authors
Sutti, S., Bruzzì, S., Heymann, F., Liepelt, A., Krenkel, O., Toscani, A., Ramavath, N., Cotella, D., Albano, E., & Tacke, F.
Affiliations
  • Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
  • Charité – Universitätsmedizin Berlin (DE)
  • Universitätsklinikum Aachen (DE)
Corresponding author
Sutti, Salvatore
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2019-09-18
Volume
8
Issue
9
Pages
1099
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells8091099
PMC
PMC6770190
OpenAlex
W2974072335
Cited by
34
References
38
Citations by year
2025: 2 · 2024: 11 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 5 · 2018: 1
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
Funders
  • German Research Foundation ((DFG Ta434/3-1, Ta434/5-1 and SFB/1382))
  • University of East Piedmont (Fondi Ricerca Locale)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
CX3CR1, fractalkine, monocyte-derived dendritic cells, liver inflammation, carbon tetrachloride, methionine-choline-deficient diet, steatohepatitis, dendritic cell differentiation, chronic liver disease, myeloid cells
MeSH terms
CX3C Chemokine Receptor 1, Animals, Carbon Tetrachloride, Cell Differentiation, Dendritic Cells, Disease Models, Animal, Inflammation, Liver, Male, Mice, Inbred C57BL, Mice, Transgenic, Monocytes, Mice, Chemical and Drug Induced Liver Injury

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