Researchers uncover how T and B cells learn to attack liver cells in metabolic diseases

By The Science Advisory Board staff writers

August 19, 2022 -- Weill Cornell Medicine researchers have identified a protein that is instrumental in activating both T and B cells to attack liver cells in metabolic disorders, helping to further understanding of the dynamics underlying liver damage that can accompany type 2 diabetes and obesity.

In their study, published August 19 in the journal Science Immunology, researchers mimicked human metabolic diseases by genetically altering mice or feeding them a high-fat, high-sugar diet.

Researchers found that a protein, called PDIA3, activates both B and T cells. When under stress, they discovered that cells make more PDIA3, which travels to their surfaces, where it becomes easier for the immune system to attack.

"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," lead investigator Dr. Laura Santambrogio, PhD, professor of radiation oncology and of physiology and biophysics, and associate director for precision immunology at the Englander Institute for Precision Medicine at Weill Cornell Medicine, said in a statement. "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."

Although their experiments were conducted in mice, researchers say a similar dynamic appears to be at play in humans. They 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.

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