people with type 1 diabetes, the body destroys certain cells in the
pancreas because it mistakes them for foreign invaders. Researchers
in Switzerland believe they have found one of the long-sought
triggers of this attack.
The cells that are destroyed, called beta cells, normally
produce certain proteins in packages called exosomes. The new study
found that, when the cells are in trouble, such as after an
infection or other stressful event, these packages are decorated
with chemical warning signals that may act as homing beacons that
lure immune cells.
"When beta cells are subjected to stress, the exosomes are
released at higher levels and now contain proteins that signal
danger to alert the immune system," said one of the study's authors
Steinunn Baekkeskov, a biochemist at the Swiss Federal Institute of
Technology in Lausanne, Switzerland.
The new findings could provide a means to shut off the wayward
immune system, thereby preventing the development of type 1
diabetes in people who are at very early stages of the
In an ongoing, decades-long study, scientists have monitored the
family members of people with type 1 diabetes (who are at increased
risk of developing it themselves), and found evidence that the
autoimmune assault begins before people show symptoms.
Early on in the course of the condition, people have high levels
of certain antibodies that bind to pancreatic proteins found in the
beta cells. If a person tests positive for two or more antibodies
to these proteins, it virtually guarantees that he or she will
develop the disease eventually, even if the person has no symptoms
for years, according to a 2015 study in the journal Diabetes
These findings have raised researchers' hopes of intervening
early, to shut off the immune attack in people with antibodies
before too many beta cells are killed, Dr Baekkeskov said.
"Antibody-positive individuals, who have not yet developed
clinical disease, are candidates for immune preventive therapy to
block beta-cell destruction and prevent the development of type 1
diabetes," Dr Baekkeskov said.
But researchers still didn't know how these beta-cell proteins
first encountered the immune cells that trigger autoimmunity.
To answer that question, Dr Baekkeskov and her colleagues
analysed the exosomes from both human and rat beta cells. They
found that the exosomes carried the beta-cell proteins recognized
by the antibodies. In addition, these exosomes seemed to attract
immune cells and activate them, she said.
When the cells were under stress, the exosomes were decorated
with chaperone proteins, or special molecules that take newly made
proteins and help them fold or travel through the cell to their
final destination, Dr Baekkeskov said.
However, in this case, the chaperone proteins were not benign;
they acted as a flashing emergency light that signals danger to the
From there, immune molecules flag the molecules as dangerous,
the researchers hypothesized in the November 21, 2016, issue of the
It's possible that inflammation, such as the response to an
infection or other assault, stresses the beta cells and causes them
to release exosomes marked with these warning signals, the
At that point, the immune system launches an unrelenting
assault, and the immune system's long memory makes it very hard to
shut off the attack. (The study doesn't address whether there may
be many other initial triggers for beta-cell destruction.)
The new findings suggest a way to reprogram the immune system.
One possibility would be to engineer an exosome mimic that can lure
immune cells to them.
These exosomes could be covered with chemical signals that lure
the beta-cell-killing immune cells and block or kill them, Dr