ArticleHepatology (Baltimore, Md.)2015
Chemokine (C-X-C motif) ligand 13 promotes intrahepatic chemokine (C-X-C motif) receptor 5+ lymphocyte homing and aberrant B-cell immune responses in primary biliary cirrhosis.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
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- The CXCL13 hub in obesity-related metabolic inflammation: regulation of spatiotemporal heterogeneity and targeted strategies.The Journal of endocrinology · 2026Review
- Methylation and expression dynamics in broiler liver followingJournal of veterinary research · 2026Article
- Molecular mechanisms underlying T cell subset imbalance and precision therapeutic targets in primary biliary cholangitis.Frontiers in pharmacology · 2026Review
- Immune cell remodelling and the peribiliary immune niche in primary biliary cholangitis: from initiation to chronicity.eGastroenterology · 2026Review
- CXCL13 and IL-33 as Immunomodulatory Adjuvants Combined with Respiratory Syncytial Virus Fusion (RSV F) Protein to Enhance Mucosal RSV Vaccination.Infection and drug resistance · 2026Review
- Elevated Serum Soluble Tim-3 in Primary Biliary Cholangitis: Lack of Correlation with Cytokines, Chemokines, and Clinical Parameters.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2025Article
- The impact of T cells on immune-related liver diseases: an overview.Inflammation and regeneration · 2025Review
- Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression.Gut and liver · 2025Article
- Common pathological mechanisms and therapeutic strategies in primary Sjogren's syndrome and primary biliary cholangitis: from tissue immune microenvironment to targeted therapy.Frontiers in immunology · 2025Review
- ChIP-seq analysis found IL21R, a target gene of GTF2I-the susceptibility gene for primary biliary cholangitis in Chinese Han.Hepatology international · 2024Article
- Gut Microbiome and Hepatic Transcriptomic Determinants of HCC Development in Mice with Metabolic Dysfunction-Associated Steatohepatitis.Journal of hepatocellular carcinoma · 2024Article
- Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?Frontiers in immunology · 2023Review
- The progress of autoimmune hepatitis research and future challenges.Open medicine (Warsaw, Poland) · 2023Review
- The Role of Inflammation in Cholestatic Liver Injury.Journal of inflammation research · 2023Review
- Antidepressants cheer up hepatic B1 B cells: Hope for the treatment of autoimmune liver diseases?Frontiers in immunology · 2022Article
- Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases.Frontiers in immunology · 2022Review
- The Role of B Cells and B Cell Therapies in Immune-Mediated Liver Diseases.Frontiers in immunology · 2021Review
- CD19Mediators of inflammation · 2020Article
- Protective role of melatonin in early-stage and end-stage liver cirrhosis.Journal of cellular and molecular medicine · 2019Review
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
unlabelledThe serological hallmark of primary biliary cirrhosis (PBC) is the presence of high titer and specific antimitochondrial antibodies (AMAs). Although there is no global immune defect in patients with PBC, there is widespread dysregulated B-cell function, including increased sera levels of immunoglobulin M and enhanced B-cell responses to cytosine-phosphate-guanine stimulation. The mechanisms involved in this B-cell dysfunction have remained unknown. To address this issue, we focused on identifying the frequencies of B-cell subsets in patients with PBC and the mechanisms that lead to B-cell dysregulation, including the relationships with chemokine (C-X-C motif) receptor 5 (CXCR5)(+) CD4(+) T cells. Herein, we report that elevations of both serum and intrahepatic interleukin-21 (IL-21) were found in patients with PBC and, in particular, promoted B-cell proliferation, signal transducer and activator of transcription 3 phosphorylation and AMA production in vitro. More important, upon stimulation with recombinant E2 subunit of pyruvate dehydrogenase complex, CXCR5(+) CD4(+) T cells in PBC produced higher levels of IL-21 than healthy controls. Additionally, sorted CXCR5(+) CD4(+) T cells increased production of AMAs by autologous CD19(+) B cells. Indeed, elevated expression of intrahepatic chemokine (C-X-C motif) ligand 13 (CXCL13), a key chemokine of CXCR5(+) cells, was uniquely found within the portal tracts in PBC, accompanied by infiltrates of CD4(+) , CXCR5(+) , CD19(+) , and CD38(+) cells.
conclusionCXCL13 promotes aggregation of CD19(+) B cells and CXCR5(+) CD4(+) T cells, which directs the aberrant AMA response by IL-21. These data have implications for potential immunotherapy and also reflect the unique lymphoid biology in liver of PBC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.