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Immune-Liver Axis—from Disease Pathogenesis to Therapeutic Target

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 1616

Special Issue Editor


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Guest Editor
Department of Gastroenterology and Hepatology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland
Interests: liver diseases; liver cirrhosis; liver failure; liver diseases and immunology; gastrointestinal diseases; non-alcoholic fatty liver disease; hepatorenal syndrome; viral hepatitis
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Special Issue Information

Dear Colleagues,

Numerous liver disorders are closely associated with inflammation and immune alterations, although the majority of the pathways that are involved are still unknown. Investigations conducted in recent years shed some light on the inflammatory cascade in liver cell injury, and the immune–liver axis has gained increased attention. The results of multiple studies have demonstrated that it may induce not only parenchymal damage, but also hepatic fibrosis and subsequent conversion to liver cirrhosis. The anatomical structure and function of the liver can facilitate and modulate the immune response to pathogens but can also lead to antigen-specific tolerance. The unique structure of the hepatic sinusoidal endothelium, which lacks a basement membrane and has fenestrations, leads to the exposure and provides direct contact between blood lymphocytes and antigens presented by endothelial or immune cells (such as hepatic macrophages, so-called Kupffer cells, and dendritic cells). Therefore, different etiologic factors causing damage to either hepatocytes or bile ducts may alter the intrahepatic immune balance and trigger an inflammatory response such as auto-aggression.

The aim of the present Special Issue is to highlight the impact of immunity and inflammation on the pathogenesis and clinical outcome of liver diseases of different origins, as well as providing a possible contribution to the prevention of disease progression and treatment. We are honored to invite researchers to submit all types of papers including original, narrative, and systematic reviews to this Special Issue in order to widen our knowledge of immune–hepatic interactions and their implications for human health. Papers are expected to be submitted before the end of May 2025.

Kind regards,

Prof. Dr. Beata Kasztelan-Szczerbińska
Guest Editor

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Keywords

  • immune response
  • inflammation
  • liver disease
  • liver injury
  • liver cirrhosis
  • immune-related liver disease
  • alcohol-related liver disease
  • metabolic dysfunction-associated steatotic liver disease (MASLD)
  • Wilson’s disease
  • hemochromatosis
  • liver cancer

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Published Papers (2 papers)

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Research

21 pages, 1220 KB  
Article
Diagnostic and Prognostic Potential of CXCL9 and CXCL10 Chemokines in Alcohol-Associated Liver Disease
by Agnieszka Szczerbinska, Jacek Rolinski, Agata Surdacka and Halina Cichoz-Lach
Int. J. Mol. Sci. 2025, 26(23), 11717; https://doi.org/10.3390/ijms262311717 - 3 Dec 2025
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Abstract
Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of [...] Read more.
Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of inflammation and contribute to the inflammatory cascade that may result in organ failure. We aimed to investigate blood concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 chemokines and their diagnostic and prognostic significance in patients with ALD. In a prospective observational study, 88 individuals were recruited, including 63 patients with ALD (44 men and 19 women, aged 48.49 ± 10.88) and 25 healthy control volunteers matched for age, sex, and ethnicity. In blood samples, concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 were measured using immunoenzymatic ELISAs. Correlations were examined between CXCL levels and (a) traditional inflammatory markers (C-reactive protein, white blood cell count, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio-NLR) and (b) liver dysfunction severity scores: Child–Turcotte–Pugh (CTP), MELD-NA, MELD 3.0, and modified Maddrey’s discriminant function (mDF). Patients’ survival within 30 days of hospital admission was recorded for analysis. CXCL capabilities in predicting the severity of liver dysfunction and ALD outcome were validated. ALD patients showed significant systemic upregulation of all studied chemokines compared to the control group. Patients with advanced liver disease, classified as MELD-Na ≥ 20, MELD3.0 > 19, and CTP class C, as well as poor short-term outcomes, presented with significantly higher CXCL9 and CXCL10 levels compared to their counterparts. ALD non-survivors had significantly higher concentrations of all studied CXCLs in comparison to controls. Positive correlations between CXCL16 and CRP, leukocytosis, neutrophils, and NLR were confirmed (0.67; 0.46; 0.48; 0.54, respectively). Although none of the chemokines correlated with ALT activity, CXCL9, CXCL10, and CXCL16 showed positive correlations with bilirubin and alkaline phosphatase and inverse correlations with albumin levels. Our findings revealed the diagnostic and prognostic value of the studied CXCLs in ALD. In particular, CXCL9 and CXCL10 may have potential for discrimination of severe liver dysfunction and poor short-term prognosis. Further multicenter studies are required to confirm our results. Full article
(This article belongs to the Special Issue Immune-Liver Axis—from Disease Pathogenesis to Therapeutic Target)
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18 pages, 2889 KB  
Article
Exploring the Bone–Liver Axis: Impact of Acute Ethanol Intoxication on Post-Traumatic Liver Inflammation and Damage Following Femur Fracture
by Jasmin Maria Bülow, Helen Rinderknecht, Nils Becker, Kernt Köhler, Alessa Wagner, Yuntao Yang, Katrin Bundkirchen, Claudia Neunaber and Borna Relja
Int. J. Mol. Sci. 2025, 26(10), 4923; https://doi.org/10.3390/ijms26104923 - 21 May 2025
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Abstract
Bone fracture activates the immune system and induces inflammation crucial for fracture healing but may also affect trauma-distant organs like the liver. Acute alcohol intoxication (AAI) dysregulates immune responses and affects organ damage post-trauma. However, the bone–liver axis and alcohol’s role in this [...] Read more.
Bone fracture activates the immune system and induces inflammation crucial for fracture healing but may also affect trauma-distant organs like the liver. Acute alcohol intoxication (AAI) dysregulates immune responses and affects organ damage post-trauma. However, the bone–liver axis and alcohol’s role in this process remain poorly understood. This study explores liver inflammation and damage following fracture, with and without prior AAI. Twenty-four male C57BL/6J mice were randomly assigned to four groups (n = 6) and received either NaCl (control) or 35% ethanol via gavage. Mice underwent femur osteotomy with external fixation or sham surgery. After 24 h, liver damage was assessed using hematoxylin–eosin and activated caspase-3 staining. Liver inflammation was evaluated through CXCL1 and polymorphonuclear leukocyte (PMNL) immunostaining, cytokine gene and protein expression analyses, and immune cell profiling in the liver via flow cytometry. Western blotting assessed NF-κB and Wnt signaling. Neither fracture alone nor with AAI caused significant liver damage. However, fracture significantly increased PMNL infiltration and altered monocyte populations, effects that were amplified by AAI. The hepatic neutrophil-to-monocyte ratio significantly decreased after fracture and was absent in the fracture AAI group. CXCL1 increased post-fracture, while MCP-1 and IL-10 decreased significantly, with AAI further significantly amplifying these changes. Wnt1 and Wnt3a levels increased significantly after fracture and were further strongly elevated by AAI. AAI completely abolished fracture-induced significant β-catenin reduction and significantly increased its phosphorylation, effects that potentially involve an AAI-induced β-catenin stabilization as well as its increased degradation. NF-κB activation was significantly decreased, while A20 expression significantly increased after fracture and AAI. Fracture influences the inflammatory liver response and signaling pathways, effects which were further modulated by AAI. Full article
(This article belongs to the Special Issue Immune-Liver Axis—from Disease Pathogenesis to Therapeutic Target)
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