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-
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
Richard Flavell, professor and chairman of Immunobiology at the Yale School of
Medicine, investigated whether TGF-
Beta 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-
Beta was blocked at different places in the immune system. They found
that when they blocked TGF-
Beta 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-
Beta is removed could all be explained by T cells," said
Flavell. "Now we know that TGF-
Beta control of DC's is important to
prevent autoimmunity."
The PNAS study may explain why efforts to spur
TGF-
Beta activity only in T cells have had limited effects in treating
autoimmune diseases, Flavell said.
The authors also speculated that
bolstering TGF-
Beta 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
Yale
University
