Scientists detect the target of immune attacks on liver cells

The molecule that attacks the liver when fat builds up in the organ has been detected by a team of academics.

Research conducted by Weill Cornell Medicine has identified how liver damage is associated with obesity and type 2 diabetes.

As part of the trial, the scientists genetically altered mice or fed them a high-fat, high-sugar diet so they presented signs of these two metabolic conditions.

They analysed alterations within the arm of the mice’s immune system that protects them from certain types of harm.

Top author Dr Laura Santambrogio said:For the longest time, people have been wondering how T and B cells learn to attack liver cells, which are under increased metabolic stress due to a high fat high sugar diet.

“We have identified one protein – probably the first of many – that is produced by stressed liver cells and then recognised by both B and T cells as a target.”

Activating the immune system further worsens the damage already caused within the liver in people living with obesity and type 2 diabetes, the study has reported.

The liver of a person with the two metabolic conditions stores a large amount of fat, putting the cells at risk of feeling stressed.

This can trigger the development of non-alcoholic steatohepatitis, which is otherwise known as fatty liver disease.

Examining the activity of another type of immune cell, called dendritic cells, led the researchers to a protein, called PDIA3, that they found activates both B and T cells. Stressed cells make more PDIA3, making it easier for the immune system to attack.

The researchers found elevated levels of antibodies for PDIA3 antibodies in blood samples from people with type 2 diabetes, as well as in autoimmune conditions affecting the liver and its bile ducts.

Dr Santambrogio said: “The connection with diet and a decrease in fatty liver disease was already well established.

“We have added a new piece to the puzzle by showing how the immune system starts to attack the liver.”

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