Cx3cl1 (Fractalkine): A Signpost for Biliary Inflammation in Primary Biliary Cirrhosis
Open accessAbstract
Improvements in the treatment of primary biliary cirrhosis (PBC) may depend upon dissection of mechanisms that determine recruitment of mononuclear cells to intralobular bile ducts, including the role of the chemokine-adhesion molecule CX3CL1 (fractalkine). We submit that there are unique interactions between intrahepatic biliary epithelial cells (BECs), endothelial cells (ECs), liver sinusoidal endothelial cells (LSECs), and liver-infiltrating mononuclear cells (LMCs), and that such interactions will in part dictate the biliary-specific inflammatory response. To address this, we studied fresh explanted livers from pretransplantation patients with PBC and with inflammatory liver disease due to viral infection (disease controls) and biopsy material from patients with a discrete liver tumor (normal controls). Using this clinical material, we isolated and stimulated BECs, ECs, LSECs, and LMCs with a panel of Toll-like receptor ligands. We also studied the interactions of these cell populations with LMCs with respect to adhesion capability and production of tumor necrosis factor α (TNF-α). Finally, we used fresh biopsy samples to evaluate mononuclear cells around intrahepatic biliary ductules using monoclonal antibodies specific to CD68 or CD154, markers for monocytes/macrophages, and activated T cells, respectively. Conclusion: There are common properties of ECs, LSECs, and BECs, whether derived from PBC or viral hepatitis, but there are also significant differences, particularly in the potential in PBC for LMCs to adhere to ECs and BECs and to produce TNF-α; such properties were associated with augmented CX3CL1 production by BEC from PBC liver. The processes defined herein suggest potential novel biotherapies for biliary specific inflammation. (Hepatology 2009.)
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Myeloid cells, i.e., monocytes and macrophages, play an important role in the pathogenesis of primary biliary cholangitis (PBC).
“Myeloid cells, i.e., monocytes and macrophages, represent a key component of innate and adaptive immune systems and play an important role in the pathogenesis of PBC.”
From A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression (2023) · cites this paper as [34]
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- Authors
- Shimoda, S., Harada, K., Niiro, H., Taketomi, A., Maehara, Y., Tsuneyama, K., Kikuchi, K., Nakanuma, Y., Mackay, I. R., Gershwin, E. M., & Akashi, K.
- Affiliations
- Kyushu University (JP)
- Kanazawa University (JP)
- University of Toyama (JP)
- Teikyo University (JP)
- Monash University (AU)
- University of California, Davis (US)
- Corresponding author
- Shimoda, Shinji
- ORCID
- Venue
- Hepatology
- Published
- 2010-02
- Volume
- 51
- Issue
- 2
- Pages
- 567-575
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC2911959
- OpenAlex
- W1974756099
- Cited by
- 108
- References
- 33
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 9 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 9 · 2016: 2 · 2015: 7 · 2014: 6 · 2013: 8 · 2012: 5
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK039588, R01DK039588)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- primary biliary cirrhosis, fractalkine, biliary tract inflammation, cholangiocytes, liver sinusoidal endothelial cells, endothelial cells, mononuclear cell recruitment, cell adhesion, TNF-α, Toll-like receptor activation, CD68, CD154, monocytes/macrophages, activated T cells, chemokines
- MeSH terms
- Epithelial Cells, Humans, Inflammation, Liver, Liver Cirrhosis, Biliary, Monocytes, Chemokine CX3CL1
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