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Cited by 61Liver Diseases and ImmunityImmune cells in cancerLiver physiology and pathology

A functional characteristic of cysteine‐rich protein 61: Modulation of myeloid‐derived suppressor cells in liver inflammation

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Zhang, Haiyan, Lian, Min, Zhang, Jun, Bian, Zhaolian, Tang, Ruqi, Miao, Qi, Peng, Yanshen, Fang, Jingyuan +5 more·2018·Hepatology
DOI 10.1002/hep.29418
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Abstract

There is increasing awareness of the immunologic roles of liver mononuclear populations, including myeloid‐derived suppressor cells (MDSCs). We took advantage of a large well‐defined cohort of 148 patients with liver inflammation and 45 healthy controls to focus on the qualitative and quantitative characteristics of MDSCs. We investigated the frequency, phenotype, and functional capacities of MDSCs by using peripheral blood MDSCs in a cohort of 55 patients with primary biliary cholangitis (PBC), 40 with autoimmune hepatitis, 39 with chronic hepatitis B, 14 with nonalcoholic fatty liver disease, and 45 healthy controls. This was followed by a liver‐targeted determination in 27 patients with PBC, 27 with autoimmune hepatitis, 20 with chronic hepatitis B, 14 with nonalcoholic fatty liver disease, and 6 controls. We then focused on mechanisms of this expansion with PBC as an example, using both ursodeoxycholic acid‐naive and treated patients. HLA‐DR −/low CD33 + CD11b + CD14 + CD15 − monocytic MDSCs were elevated in diseases characterized by liver inflammation compared to healthy controls. Using PBC as a focus, there was a significant correlation between levels of circulating MDSCs and disease‐related biochemical markers (alkaline phosphatase, total bilirubin). We found higher amounts of MDSCs in patients with PBC who were responsive to ursodeoxycholic acid. MDSCs from PBC were found to manifest a potent immunosuppressive function. There was a significant correlation in the accumulation of hepatic MDSCs in the inflamed lesions of PBC with histologic changes, such as fibrosis. We also found that cysteine‐rich protein 61 (CCN1), a highly expressed protein in impaired cholangiocytes and hepatocytes, contributes to MDSC expansion and MDSC inducible nitric oxide synthase‐associated immune suppression. Conclusion : CCN1 modulates expansion and a suppressive function of MDSCs. Our data highlight the potential functions of CCN1 on MDSCs and suggest therapeutic implications in inflammatory liver diseases. (H epatology HEPATOLOGY 2018;67:232‐246).

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  • Myeloid-derived suppressor cells (MDSCs) are expanded in the periphery of PBC patients and exert immunosuppressive effects on T cell proliferation.

    “We have previously shown that myeloid-derived suppressor cells (MDSCs), a group of immature myeloid cells, were expanded in the periphery of PBC patients and exerted immunosuppressive effects on T cell proliferation38.”

    From A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression (2023) · cites this paper as [38]

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Authors
Zhang, H., Lian, M., Zhang, J., Bian, Z., Tang, R., Miao, Q., Peng, Y., Fang, J., You, Z., Invernizzi, P., Wang, Q., Gershwin, M. E., & Ma, X.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine,Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease,Shanghai,China
  • University of Milano-Bicocca (IT)
  • University of California, Davis (US)
Corresponding author
  • Wang, Qixia
  • Gershwin, M. Eric
  • Ma, Xiong
ORCID
Venue
Hepatology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-11-17
Volume
67
Issue
1
Pages
232-246
ISSN
  • 0270-9139 (ISSN-L)
  • 1527-3350
DOI
10.1002/hep.29418
OpenAlex
W2742718825
Cited by
61
References
7
Citations by year
2026: 4 · 2025: 5 · 2024: 18 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 5
FWCI
2.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
Funders
  • National Natural Science Foundation of China (#81400608, 81570511, #81300299, 81620108002, #81421001, 81325002)
  • Shanghai Municipal Population and Family Planning Commission
Topics
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
cysteine-rich protein 61, CYR61, myeloid-derived suppressor cells, liver inflammation, primary biliary cirrhosis, autoimmune hepatitis, chronic hepatitis B, non-alcoholic fatty liver disease, ursodeoxycholic acid, immunosuppression, inducible nitric oxide synthase, liver fibrosis, cholangiocytes, hepatocytes
MeSH terms
Myeloid-Derived Suppressor Cells, Biopsy, Needle, Cells, Cultured, Female, Humans, Immunohistochemistry, Male, Reference Values, Severity of Illness Index, Biomarkers, Chi-Square Distribution, Case-Control Studies, Hepatitis, Autoimmune, Hepatitis B, Chronic, Kaplan-Meier Estimate, Cysteine-Rich Protein 61, Non-alcoholic Fatty Liver Disease

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