Newly discovered gene could provide targets for diabetes therapies

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Newly discovered gene could provide targets for diabetes therapies

Published: Wednesday, 1-Jun-2005

The Juvenile Diabetes Research Foundation (JDRF) has announced 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. The

finding was made in the laboratory of Goodnow, Ph.D., at

the Curtin School of Medical Research at Australian National

University in Canberra, Australia.

According to Dr. Insel, Executive Vice President of Research

for JDRF, " 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 a molecule called

ICOS (for " inducible co-stimulatory " ), 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 auto-reactive 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 them

with ICOS levels in those without the disease.

" This finding is a very satisfying validation for me and my team, " said

Dr. Goodnow. " 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 it's

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. "

http://www.jdrf.org