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Stanford study identifies cellular mechanism that causes lupuslike symptoms in mice
Date:10/18/2009

STANFORD, Calif. Macrophages, the scavenger cells of the body's immune system, are responsible for disposing of dying cells. Stanford University School of Medicine researchers have identified one pathway in this important process in mice that, if disrupted, causes a lupuslike autoimmune disease.

The findings could lead to both a better understanding of the cause of lupus in humans and potential drug treatments for the disorder, which affects an estimated 1.5-2 million people in the United States.

"Just like in mice, in humans, if you don't clear the dying cells, then that predisposes you to lupus," said Lata Mukundan, PhD, a Stanford research associate and one of the first authors of the study to be published online in Nature Medicine Oct. 18. "If you look at patients with lupus, they have an inability to clear those dead cells."

Added Ajay Chawla, MD, PhD, assistant professor of endocrinology and senior author of the study: "The clearing away of dying cells is important. If they're not cleared away, they can provide antigens against ourselves, leading to development of autoimmunity."

Lupus is an autoimmune disease in which the body's system attacks its own cells. The chronic inflammation causes symptoms that can resemble other types of arthritis and rheumatic diseases, affecting the skin, heart, lungs, kidneys, joints and nervous system. The cause is unknown.

Mukundan, Chawla and their colleagues have uncovered one of the pathways by which macrophages sense and silently dispose of these dying cells a naturally-occurring process not previously understood by conducting lab experiments in vitro with mouse and human macrophages, as well as in genetically engineered mice.

Researchers hypothesized that a molecule in the nucleus of cells called PPAR-delta plays a pivotal role in orchestrating the timely disposal of dying cells by macrophages, the white blood cells that swallow and digest cellular debris
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Contact: Tracie White
traciew@stanford.edu
650-723-7628
Stanford University Medical Center
Source:Eurekalert

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