REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1655287
This article is part of the Research TopicInnovative Insights into Pattern Recognition and Signaling in Innate ImmunityView all 10 articles
Innate immunity of bile and cholangiocytes in Primary Biliary Cholangitis
Provisionally accepted
- 1The Second Affiliated Hospital of Kunming Medical University, Kunming, China
- 2Kunming Medical University, Kunming, China
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Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by immune-mediated destruction of intrahepatic bile ducts. This review synthesizes current points on the critical role of innate immunity-specifically involving cholangiocytes, bile components, and associated immune cells. The function of Cholangiocytes are not merely as passive targets but also active immuno-modulators, via Toll-like receptors (TLRs), presenting antigens, and recruiting immune cells. Dysregulation of bile acid signaling through receptors like TGR5 disrupts immune homeostasis, while the apoptosis of biliary epithelial cells releases antigens (e.g., PDC-E2), triggering aberrant innate and adaptive immune responses. Innate lymphoid cells (ILCs), natural killer (NK) cells, and macrophages exhibit altered frequencies and functions in PBC, contributing to chronic inflammation and fibrosis by cytokines, such as IL-17, IFNγ. Biliary microbiota dysbiosis has been illustrated the interactions within the gut-liver axis by promoting bacterial translocation, modifying bile acid metabolism, and activating innate immune pathways. However, current therapies, including ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), target cholestasis primarily and prompts immune regulation inadequately. Therefore, innate immune targets such as RIPK2 inhibition, IL-1 blockade, TIM-3 modulation, and mesenchymal stem cell therapy.Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as the prognostic indices which correlate with the progression of auto-inflammation.Therapeutic precision requires deeper thoughts of the gut-biliary-immune networks and the senescence for cholangiocyte, it will pave the way for targeted interventions further.
Keywords: Kunming Yunnan, 650000, P.R. China) Primary Biliary Cholangitis (PBC), innate immunity, Biliary Tract, cholangiocyte, Therapeutic target, Prognostic assessment
Received: 27 Jun 2025; Accepted: 05 Sep 2025.
Copyright: © 2025 Chen, Sun, Hu and Wenlin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tai Wenlin, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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