Researchers Discover New Trigger for Autoimmune Diseases

Investigators have discovered a new way autoimmune diseases such as multiple sclerosis (MS) can be triggered.

Scientists have long known the molecule TGF-beta (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 Dr. Richard Flavell, professor and chairman of immunobiology at the Yale University School of Medicine (New Haven, CT, USA), investigated whether TGF-Beta might also influence activity of other immune system cells as well.

Dr. Flavell and his colleagues engineered mice in which TGF-beta was blocked at different places in the immune system. They discovered that when they blocked TGF-beta in dendritic cells (DCs), the mice developed lesions on myelin sheathing of central nervous system cells, the principal characteristic of MS. "Previous work suggested that the immune dysfunction seen when TGF-beta is removed, could all be explained by T cells,” said Dr. Flavell. "Now we know that TGF-beta control of DCs is important to prevent autoimmunity.”

The investigators reported their findings in the July 28, 2008, issue of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS). The PNAS study may explain why efforts to activate TGF-beta activity only in T cells have had limited effects in treating autoimmune diseases, according to Dr. Flavell. The researchers also speculated that enhancing TGF-beta activity on dendritic cells might have a potentially therapeutic effect on patients with MS and other autoimmune diseases.

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Yale University School of Medicine