Scientists decipher how the immune system induces liver damage during hepatitis

November 8, 2013, Centro Nacional de Investigaciones Oncologicas (CNIO)
This is an inflamed liver containing immune cells expressing AP-1 protein (brown). Credit: CNIO

Viral infections are the primary cause of liver inflammation or hepatitis, affecting hundreds of millions of people all over the world, and they represent a public health problem worldwide. The acute condition can cause irreversible damage to the liver, and if not cured can become chronic, leading to serious diseases such as cirrhosis or cancer.

A study published today in the online edition of The Journal of Clinical Investigation, and carried out by Erwin Wagner's team, Director of the BBVA Foundation-CNIO Cancer Cell Biology Programme and holder of an ERC Advanced Grant, shows how the immune system 'attacks' during hepatitis by using the AP-1 gene JunB.

Latifa Bakiri, one of the study's authors and a researcher in Wagner's laboratory details: "The activation of the JunB/AP-1 gene in a subset of , called NK cells, increases the production of interferon-gamma that attacks liver cells while the organ is suffering from hepatitis".

With this discovery, the study's authors propose a new mechanism by which AP-1 acts as a double-edged sword in the liver: it's a first line of defence against viruses that cause the disease, but also encourages depending on the diet or genetics of the patient.

"The balance of these signals is fundamental to the understanding of the pathogenesis of inflammatory liver disease and to design new therapeutic approaches to reverse this disease", says Wagner.

NK-type immune cells are also part of the micro-environment surrounding tumours. Researchers point out in the discussion of the article that a better knowledge of these cells may be vital for designing immune-therapies that specifically target tumour cells.

Explore further: CNIO researchers discover a new regulator of drug detoxication

More information: JUNB/AP-1 controls IFN-γ during inflammatory liver disease. Martin K. Thomsen, Latifa Bakiri, Sebastian C. Hasenfuss, Rainer Hamacher, Lola Martinez, Erwin F. Wagner. The Journal of Clinical Investigation (2013). DOI: 10.1172/JCI70405

Related Stories

CNIO researchers discover a new regulator of drug detoxication

October 11, 2013
Drug abuse and alcohol are some of the most frequent causes of liver damage, particularly in developed countries. Such kind of liver damage can cause irreversible liver failure and even cancer. Researchers from the Spanish ...

New study to combat the most common form of liver cancer

October 12, 2012
Scientists at the University of Southampton are to investigate the best way to use natural killer cells (NK) to target the most common form of liver cancer.

Liver tropism is key for B cell deletion immunotherapy

November 1, 2013
Antibodies against the B cell surface protein CD20 have been used successfully to treat B cell-mediated autoimmune diseases and lymphomas. Antibody binding receptors, called Fc receptors, on other immune cells bind anti-CD20 ...

Better insights into treating hepatitis C

October 23, 2013
With nearly 200 million infected people worldwide, hepatitis C virus (HCV) represents a significant public health issue. One of the most important challenges is that although the immune system seems to be responsible for ...

Scientists reduce progression of one of the most aggressive skin cancers in mice

September 27, 2013
The c-Fos oncogene has traditionally been linked to cellular activities related to cancer, such as cell division, differentiation—conversion from one cell type to another—or survival. Any alteration of these activities ...

A novel oncogenic network specific to liver cancer initiation

October 7, 2012
Researchers headed by Erwin Wagner, the Director of the BBVA Foundation-CNIO Cancer Cell Biology Programme at the Spanish National Cancer Research Centre (CNIO), have deciphered how a stress-inducible gene regulator, AP-1, ...

Recommended for you

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

How the immune system's key organ regenerates itself

January 15, 2018
With advances in cancer immunotherapy splashing across headlines, the immune system's powerful cancer assassins—T cells—have become dinner-table conversation. But hiding in plain sight behind that "T" is the organ from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.