Virginia University: Hot on the heels of discovering a protective form of immune response
to spinal cord injury, researchers at the University of
Virginia School of Medicine have pinpointed the biological trigger
for that response – a vital step toward being able to harness the
body’s defenses to improve treatment for spine injuries, brain trauma,
Alzheimer’s disease and other neurodegenerative conditions.
The trigger for the immune response, the molecule interleukin-33, is
concentrated in what is known as “white matter” in the healthy brain
and spinal cord. Interleukin-33, the researchers have discovered, is
released upon injury and activates cells called glia, beginning the
body’s protective response and promoting recovery.
“It’s the first thing that tells the immune system that something’s
been damaged,” said U.Va.’s Sachin Gadani, the lead author of a new
paper outlining the discovery. “It’s how the immune system initially
knows to respond.”
The researchers aren’t sure if interleukin-33 has other roles to
play in addition to its role in injury response. “Interleukin-33 must
be important to the central nervous system. It is expressed all the
time – even in the healthy state – and we’ve only described its
activity after injury,” said Jonathan Kipnis, a professor in
the Department of Neuroscience and director of
the Center for
Brain Immunology and Glia. “From an evolutionary
perspective it makes little sense. The system produces this constantly
just in case of injury that may never come? I’d be surprised if there
was no function beyond injury. IL-33 may represent a language through
which [the central nervous system] is constantly talking with the
immune system – or, in other words, a molecular mind-body
connection.”
Kipnis noted that problems with interleukin-33 could contribute to
poor outcomes after spine or brain injuries. “It’s possible that if
there’s some problem with this molecule in patients, they will have
poor alarm signaling, and they will have very poor outcomes,” he
said.
The discovery also sheds light on previous findings connecting
interleukin-33 to Alzheimer’s disease.
“There’s a huge link,” Gadani said. “Researchers have identified a
strong connection between interleukin-33 and Alzheimer’s disease, and
our work will pave the way for future studies on this topic.”
Eventually, the findings could lead to both improved treatments and
new diagnostic tests for brain and spinal cord injury, Alzheimer’s and
other conditions.
Kipnis saluted Gadani for his contributions to the work –
contributions all the more impressive considering that Gadani is still
a graduate student in U.Va.’s Medical Scientist Training
Program.
“He came in with this idea, and from the initial idea to the final
paper, he drove the research. And he’s only in his third year of
graduate school,” Kipnis said. “Credit goes to our MST program that it
is able to recruit such a high caliber of students.”
The findings have been published online by Neuron, a premier
neuroscience journal for peer-reviewed research. The article’s authors
are Gadani, James T. Walsh, Igor Smirnov, Jingjing Zheng and
Kipnis.