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Scientists discover exciting new
immune regulator gene
Newly discovered gene could provide targets for diabetes therapies
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[JUNE 3, 2005]
NEW YORK -- The Juvenile Diabetes Research
Foundation, the world's leading charitable supporter of research
into type 1 diabetes and its complications, announced recently that
JDRF-funded researchers in Australia and the United Kingdom have
identified a gene called Roquin
that regulates the immune system and keeps harmful T cells in check.
These researchers have found that if
Roquin is even slightly flawed, autoimmune diseases such as
type 1 diabetes can develop. Discovery of this mechanism could open
the door to treatment strategies by either arresting type 1 diabetes
in its earliest stages -- before islets are destroyed -- or by
potentially making islet transplantation safer.
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The finding, which was reported in the May 26 issue of the journal
Nature, was made in the
laboratory of Christopher Goodnow, Ph.D., at the John Curtin School
of Medical Research at Australian National University in Canberra,
Australia. According to Dr. Richard Insel, executive vice
president of research for Juvenile Diabetes Research Foundation,
"Dr. Goodnow and his team are to be commended for a significant
discovery that points to a novel pathway that regulates autoimmune
responses and may possibly be exploited for the development of
therapeutics. This finding is very exciting for the field of type 1
diabetes because further research in this area could lead to
developments to prevent the onset of the disease and prevent immune
attack of regenerated or transplanted beta cells."
Roquin's specific role is to restrain the action of an
inducible co-stimulatory molecule called ICOS, which exists on the
surface of immune T cells that have been activated. Essentially,
ICOS stimulates T cells to develop into "helper cells" that promote
the immune response. If the Roquin
gene is even slightly mutated, the T cells exhibit elevated levels
of ICOS, which results in an overactive immune response that attacks
the body's own cells. Attack by autoreactive T cells is responsible
for the beta cell destruction that leads to type 1 diabetes.
Dr. Goodnow and his colleagues discovered
Roquin's role from a systematic
genetic screen for autoimmune regulators in mice. One strain of mice
developed large lymph nodes and an enlarged spleen secondary to a
mutation in the DNA sequence of the
Roquin gene, causing it to function improperly. The animals had
the kind of damage that is found in lupus, another autoimmune
disease. Due to the absence of
Roquin's defensive effect, an extraordinarily large number of
autoreactive T cells infiltrated and attacked the pancreatic beta
cells in a mouse model of diabetes.
Although the Roquin gene was
found in mice, the researchers have already identified the
corresponding gene in humans, which is nearly identical. They are
eager to begin looking at the sequence of the human
Roquin gene and ICOS levels in
people with diabetes and comparing with ICOS levels in people
without the disease.
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 "This finding is a very satisfying validation for me and my
team," Goodnow said. "We are very grateful to JDRF for having the
vision to sponsor this groundbreaking work. Moreover, it is also
worth noting that the JDRF established a partnership with the
Australian National Health and Medical Research Council to support
the work and added its funding to the Wellcome Trust's, who we were
working with to screen for lupus susceptibility genes. The combined
effort of the two funding sources made it possible to obtain the
full picture of this new gene and mechanism."
The Juvenile Diabetes Research Foundation was founded in 1970 by
the parents of children with type 1 (juvenile) diabetes -- a disease
that strikes children suddenly, makes them insulin-dependent for
life and carries the constant threat of devastating complications.
Since inception, the foundation has provided more than $800 million
to diabetes research worldwide. More than 80 percent of the
foundation's expenditures directly support research and education
about research. The Juvenile Diabetes Research Foundation mission is
constant: to find a cure for diabetes and its complications through
the support of research.
[Juvenile Diabetes Research Foundation
news release]
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