Related Experiment Video

Updated: Jan 9, 2026

Isolation of Neonatal Extrahepatic Cholangiocytes
07:54

Isolation of Neonatal Extrahepatic Cholangiocytes

Published on: June 5, 2014

10.8K

A dysregulated hepcidin-iron axis impairs antiviral immunity and induces lethal liver pathology in neonates

Yanhui Xu1, Xixi Chen2, Rongli Fang2

  • 1Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Clinical Research Center for Pediatric Infection and Immunity, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China.

Immunity
|December 9, 2025
PubMed

Insights

Rotavirus infection in newborns causes liver damage by disrupting iron regulation via type I interferon (IFN-I) and hepcidin. Folic acid supplementation showed promise in reducing liver injury and complications in infants with biliary atresia.

Area of Science:

  • Immunology
  • Hepatology
  • Neonatal Medicine

Background:

  • Systemic rotavirus (RV) infection presents a significant health risk to neonates, with its pathogenesis poorly understood.
  • Biliary atresia (BA) is a serious neonatal liver condition where RV infection may exacerbate outcomes.
  • Iron dysregulation is increasingly recognized as a factor in various inflammatory and infectious diseases.

Purpose of the Study:

  • To elucidate the pathogenesis of RV infection in neonatal liver disease.
  • To investigate the role of type I interferon (IFN-I) and hepcidin in RV-induced liver injury.
  • To explore the therapeutic potential of targeting the IFN-I-hepcidin-iron axis and folic acid supplementation in neonatal liver disease.

Main Methods:

  • Utilized RV-infected neonatal mouse models and analyzed samples from infants with biliary atresia (BA).
  • Assessed the expression of hepcidin, IFN-I signaling components, and iron-related proteins (e.g., SLC40A1).
  • Investigated the effects of blocking IFN-I-hepcidin signaling, iron chelation, and folic acid administration in vivo and in a clinical trial.

Main Results:

  • Persistent IFN-I signaling upregulated hepcidin in hepatocytes and macrophages, impairing iron excretion (SLC40A1) and causing ferroptosis.
  • Iron accumulation in myeloid cells (Kupffer cells) exacerbated RV replication and IFN-I activation.
  • Blocking IFN-I-hepcidin signaling and iron chelation mitigated RV-induced liver damage in mice.
  • Folic acid suppressed the IFN-I-hepcidin-iron axis and, in a clinical trial, reduced cholangitis and liver transplantation rates in infants with BA.

Conclusions:

  • Hepcidin-iron dysregulation is a critical mechanism in neonatal RV infection and associated liver damage.
  • Targeting the IFN-I-hepcidin-iron pathway offers a potential therapeutic strategy for neonatal RV diseases.
  • Folic acid supplementation demonstrates therapeutic efficacy in infants with BA, suggesting a role in managing RV-related neonatal liver conditions.

Keywords:
Kupffer cellsSLC40A1TREM2(+) macrophagebiliary atresiaferroptosisfolic acidhepcidin and iron regulationlipid peroxidationneonatal rotavirus infectiontype I interferon signaling

More Related Videos

A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks10:28

A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks

Published on: June 26, 2020

10.2K
Extrahepatic Bile Duct and Gall Bladder Dissection in Nine-Day-Old Mouse Neonates06:10

Extrahepatic Bile Duct and Gall Bladder Dissection in Nine-Day-Old Mouse Neonates

Published on: August 23, 2022

2.4K

Related Concept Videos

Immunodeficiency Diseases01:25

Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
1.9K
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test01:22

Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test

In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
169
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...
241
Hepatic Portal System01:21

Hepatic Portal System

The hepatic portal system, a critical part of our circulatory framework, transports nutrient-laden, deoxygenated blood from the gastrointestinal tract and spleen to the liver. This ingenious system plays an indispensable role in maintaining our body's metabolic equilibrium.
At its core, the hepatic portal vein is the result of a confluence of the superior and inferior mesenteric veins along with the splenic vein. Each of these veins has a unique role. The superior mesenteric vein is...
5.1K
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
203