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Updated: Aug 12, 2025
Long Term Intravital Multiphoton Microscopy Imaging of Immune Cells in Healthy and Diseased Liver Using CXCR6.Gfp Reporter Mice
Published on: March 24, 2015
Innate immune cell dysfunction and systemic inflammation in children with chronic liver diseases undergoing
Krupa R Mysore1, Sunil Kannanganat1, Jeremy M Schraw2
1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA; William Shearer Center for Human Immunobiology, Feigin Center, Texas Children's Hospital, Houston, Texas, USA.
Insights
Children with severe advanced liver disease (ALD) show impaired immune cells, increasing infection risk. Chronic high bile acids may cause this immune dysfunction, suggesting targeted treatments for liver transplant patients.
Area of Science:
- Immunology
- Hepatology
- Pediatric Medicine
Background:
- Advanced liver diseases (ALD) impair immune function, increasing infection susceptibility.
- Liver transplantation (LT) is a critical intervention for children with ALD.
- Understanding immune cell alterations in pediatric ALD is crucial for managing transplant outcomes.
Purpose of the Study:
- To investigate phenotypic and functional changes in monocytes and dendritic cells (DCs) in children with ALD undergoing LT.
- To correlate immune cell alterations with disease severity and clinical outcomes.
- To explore the role of bile acids in immune cell dysfunction in pediatric ALD.
Main Methods:
- Stratification of pediatric patients with ALD into mild (C1) and severe (C2) clusters based on laboratory parameters.
- Flow cytometry analysis of circulating monocyte and dendritic cell populations.
- Assessment of human leucocyte antigen DR (HLA-DR) expression and interleukin-12 (IL-12) production.
- Measurement of plasma cytokine levels and correlation with ALD parameters, including bile acids.
- In vitro experiments with bile acids and monocytes to assess IL-12 production.
Main Results:
- Children with severe ALD (C2) exhibited reduced frequencies of nonclassical monocytes and myeloid DCs.
- Monocytes and DCs in C2 showed impaired function, indicated by lower HLA-DR and reduced IL-12 production.
- Patients in C2 had a higher incidence of infections pre- and post-LT.
- Immune dysregulation in C2 was evidenced by altered pro- and anti-inflammatory cytokine profiles.
- In vitro, bile acids impaired monocyte IL-12 production in a dose-dependent manner, mirroring in vivo findings.
Conclusions:
- Children with ALD undergoing LT display innate immune dysfunction potentially linked to elevated serum bile acids.
- Identifying at-risk patients with immune deficits can enable personalized pre- and post-transplant management.
- Reducing infection-related complications in pediatric liver transplant recipients is a key goal.
Abstract:
Advanced liver diseases (ALD) can affect immune function and compromise host defense against infections. In this study, we examined the phenotypic and functional alterations in circulating monocyte and dendritic cells (DCs) in children with ALD undergoing liver transplantation (LT). Children were stratified into 2 clusters, C1 (mild) and C2 (severe), on the basis of laboratory parameters of ALD and compared with healthy pediatric controls. Children in C2 had a significant reduction in frequencies of nonclassical monocytes and myeloid DCs. Children in C2 displayed monocyte and DC dysfunction, characterized by lower human leucocyte antigen DR expression and reduced interleukin 12 production, and had an increased incidence of infections before and after LT. Children in C2 demonstrated immune dysregulation with elevations of pro- and anti-inflammatory cytokines in plasma. Alterations of innate immune cells correlated with multiple laboratory parameters of ALD, including plasma bile acids. In vitro, monocytes cultured with specific bile acids demonstrated a dose-dependent reduction in interleukin 12 production, similar to alterations in children with ALD. In conclusion, a cohort of children with ALD undergoing LT exhibited innate immune dysfunction, which may be related to the chronic elevation of serum bile acids. Identifying at-risk patients may permit personalized management pre- and post-transplant, thereby reducing the incidence of infection-related complications.
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