The Emerging Role of Macrophages in Chronic Cholangiopathies Featuring Biliary Fibrosis: An Attractive Therapeutic Target for Orphan Diseases
Open accessAbstract
Cholangiopathies are a heterogeneous group of chronic liver diseases caused by different types of injury targeting the biliary epithelium, such as genetic defects and immune-mediated attacks. Notably, most cholangiopathies are orphan, thereby representing one of the major gaps in knowledge of the modern hepatology. A typical hallmark of disease progression in cholangiopathies is portal scarring, and thus development of effective therapeutic approaches would aim to hinder cellular and molecular mechanisms underpinning biliary fibrogenesis. Recent lines of evidence indicate that macrophages, rather than more conventional cell effectors of liver fibrosis such as hepatic stellate cells and portal fibroblasts, are actively involved in the earliest stages of biliary fibrogenesis by exchanging a multitude of cues with cholangiocytes, which promote their recruitment from the circulating compartment owing to a senescent or an immature epithelial phenotype. Two cholangiopathies, namely primary sclerosing cholangitis and congenital hepatic fibrosis, are paradigmatic of this mechanism. This review summarizes current understandings of the cytokine and extracellular vesicles-mediated communications between cholangiocytes and macrophages typically occurring in the two cholangiopathies to unveil potential novel targets for the treatment of biliary fibrosis.
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Macrophages have emerged as essential players in acute and chronic liver injury and in a wide range of liver diseases including NASH and more recently also PSC.
“Macrophages have emerged as essential players in acute and chronic liver injury and in a wide range of liver diseases including NASH216 and more recently also PSC.217”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [217]
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Bernard, J. K., Marakovits, C. N., Smith, L., & Francis, H. (2023) · Seminars in Liver Disease · doi:10.1055/a-2104-9034 · Cited by 13 · see citing works
Fabris, L., Milani, C., Fiorotto, R., Mariotti, V., Kaffe, E., Seller, B., Sonzogni, A., Strazzabosco, M., & Cadamuro, M. (2022) · The FASEB Journal · doi:10.1096/fj.202101924r · Cited by 10 · see citing works
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An Integrated Pathogenetic Model of Primary Biliary Cholangitis
Kouroumalis, E., Tsomidis, I., & Voumvouraki, A. (2025) · Livers · doi:10.3390/livers5020015 · Cited by 7 · see citing works
Urinary soluble CD163 is a putative non-invasive biomarker for primary sclerosing cholangitis
Elger, T., Fererberger, T., Huss, M., Sommersberger, S., Mester, P., Stöckert, P., Gunawan, S., Liebisch, G., Loibl, J., Kandulski, A., et al. (2024) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2024.104900 · Cited by 4 · see citing works
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Mesenchymal stromal cell administration promotes macrophage-mediated bile duct regeneration
五十嵐, 崇., Kimura, N., Abé, H., Yoshida, T., Watanabe, Y., Kamimura, H., Sakamaki, A., Yokoo, T., Kamimura, K., Tsuchiya, A., et al. (2026) · Regenerative Therapy · doi:10.1016/j.reth.2026.101065 · Cited by 1 · see citing works
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- Authors
- Cadamuro, M., Girardi, N., Gores, G. J., Strazzabosco, M., & Fabris, L.
- Affiliations
- University of Padua (IT)
- Mayo Clinic (US)
- Yale University (US)
- Corresponding author
- Fabris, Luca
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2020-04-21
- Volume
- 7
- Pages
- 115-115
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC7186419
- OpenAlex
- W3015679566
- Cited by
- 19
- References
- 82
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 1
- FWCI
- 0.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Funders
- PSC Partners Seeking a Cure
- National Institutes of Health (RO1DK096096I)
- Università degli Studi di Padova
- 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
- macrophages, biliary fibrosis, primary sclerosing cholangitis, congenital hepatic fibrosis, cholangiocytes, macrophage recruitment, extracellular vesicles, cytokines, rare diseases, therapeutic target, liver fibrosis
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