Identifying the Target of Immune Attacks on Liver.

• Position: METABOLIC DISORDERS

When fat accumulates in the liver, the immune system may assault the organ. A study from Weill Cornell Medicine researchers identifies the molecule that trips these defenses, a discovery that helps to explain the dynamics underlying liver damage that can accompany type 2 diabetes and obesity.

In a study published in Science Immunology, researchers mimicked these human metabolic diseases by genetically altering mice or feeding them a high-fat, high-sugar diet. They then examined changes within the arm of the rodent's immune system that mounts defenses tailored to specific threats. When misdirected back on the body, this Immune response, which involves B and T cells, damages the organs and tissues it is meant to protect.

"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," says lead Investigator Laura Santambrogio, professor of radiation oncology and of physiology and biophysics, and associate director for precision immunology at the Englander Institute for Precision Medicine. "We have identified one protein--probably the first of many--that is produced by stressed liver cells and then recognized by both B and T cells as a target."

The activation of the immune system further aggravates the damage already occurring within this organ in people who have these metabolic conditions, she explains. In type 2 diabetes or obesity, the liver stores an excessive amount of fat, which can stress cells, leading to a condition known as nonalcoholic steatohepatitis, commonly called fatty liver disease. The stress leads to inflammation, a nonspecific immune response that, while meant to protect, can harm...