Researchers Find New Trigger for Autoimmune Diseases

Yale University researchers have discovered a new way that autoimmune diseases like multiple sclerosis (MS) can be triggered, they reported Monday in the journal Proceedings of the National Academy of Sciences.

Scientists have long known the molecule TGF-β (transforming growth factor beta) plays a pivotal role in preventing T cells from launching an attack on the body’s own tissues.

A team led by Richard Flavell, professor and chairman of Immunobiology at the Yale School of Medicine, investigated whether TGF-β might also influence activity of other immune system cells as well.

Flavell, an investigator for the Howard Hughes Medical Institute, and his colleagues engineered mice in which TGF-β was blocked at different places in the immune system. They found that when they blocked TGF-β in dendritic cells (DC’s) the mice developed lesions on myelin sheathing of central nervous system cells, the hallmark of MS.

“Previous work suggested that the immune dysfunction seen when TGF-β is removed could all be explained by T cells,” said Flavell. “Now we know that TGF-β control of DC’s is important to prevent autoimmunity.”

The PNAS study may explain why efforts to spur TGF-β activity only in T cells have had limited effects in treating autoimmune diseases, Flavell said.

The authors also speculated that bolstering TGF-β activity on dendritic cells might have a potentially therapeutic effect on patients with MS and other autoimmune diseases.

Authors on the study include Yasmina Laouar, Terrence Town, David Jeng, Elise Tran, Yisong Wan, and Vijay K. Kuchroo.

The research was supported by National Institutes of Health.

Citation: PNAS July 28, 2008