November 29, 2011
A neutrophil (yellow), the most abundant white blood cell type and the first line of defense against invading microbes, engulfs Bacillus anthracis (orange), the agent of anthrax. The bacteria break down, releasing DNA that triggers an immune response.
One in five Americans suffers from autoimmune disease, in which the immune system goes off-track and attacks the body’s own cells. Cornell researchers have identified a signaling mechanism in immune-system cells that may contribute to this mistake, opening the door for possible new therapies for autoimmune diseases such as lupus and arthritis.
Cynthia Leifer, assistant professor of microbiology and immunology in the College of Veterinary Medicine, and colleagues described the mechanism in the August issue of the European Journal of Immunology. The problem lies in what are called innate immune cells, the first responders to infection.
“Innate immune cells have internal watchdogs called TLR-9 receptors that set off alarms whenever they encounter invaders,” said Leifer. “They look for general classifying patterns [in DNA] to determine whether something is a virus, bacterium, protozoan, or part of self.”
However, some of these patterns exist both in invading organisms and the body’s own cells, so mistakes can arise.
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“We are mapping the critical regulatory mechanisms that keep these receptors from responding to self-DNA so that we can know if and how they predispose people to autoimmune disorders when they fail,” Leifer said.
Innate immune cells engulf things that look dangerous, tear them open, and release their components, including DNA. When TLR-9 receptors see DNA that identifies microbes, they send a signal to fire up more immune-system activity, including inflammation and the creation of antibodies. But before a receptor can work, enzymes in the cell must prepare it by chopping off part of the receptor molecule and leaving a part that can bind to microbe DNA.
From there, Leifer believes it’s a numbers game. If too many receptors are prepared, they may respond to the small amount of self-DNA that makes its way into immune cells, triggering an autoimmune response. So the immune cell has a regulatory mechanism, an enzyme pathway that cuts prepared receptors in a second place.
Working with cells in culture, Leifer identified this second chopping event, which cuts TLR-9 at a different site. This produces a molecule that binds to DNA, blocking it from reaching the prepared receptors, and does not send a signal.
“People without autoimmune diseases have the right balance of these two chopping events,” Leifer said. “Our studies suggest that people with a propensity for these diseases might have a defect in this pathway that allows more prepared receptors to signal for immune responses. This may be a potential target for therapies designed to help quiet those alarms.”
A second but interrelated problem Leifer has tackled involves how TLR-9 moves through an immune cell from the placewhere it is created to its working site. In earlier work she described the protein sequences in TLR-9 that act as address labels guiding where the receptor travels.
“We think they’re interrelated because if you don’t travel properly you don’t get chopped properly,” she said. “If TLR-9 ends up in the wrong place at the wrong time, it can sound a false alarm.
Leifer’s research is supported by the National Institutes of Health.
Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.
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Original Press Release:
Cornell University College of Veterinary Medicine news
http://www.vet.cornell.edu/news/leifer.cfm
Media Hits:
Cornell Chronicle
http://www.news.cornell.edu/stories/Nov11/LeiferDNA.html
Medical Xpress (PhysOrg)
http://medicalxpress.com/news/2011-11-unchecked-alarms-autoimmune-disease.html
MyScience
http://www.myscience.us/wire/how_unchecked_alarms_can_spark_autoimmune_disease-2011-cornell
Bionity
http://www.bionity.com/en/news/135431/how-unchecked-alarms-can-spark-autoimmune-disease.html
R&D Mag
ECN
Futurity
http://www.futurity.org/top-stories/false-alarm-can-spark-autoimmune-disease/
Sparks flew amid a chorus of clangs and the smell of horses as farriers, metalworkers, and equine enthusiasts converged from near and far for the 2011 Cornell Farrier Conference on the weekend of November 12-13. Organized and hosted by the College of Veterinary Medicine since 1983, the renowned conference garnered 91 attendees in its 27th year.
In September 2011 Dr. Christopher R. Byron BS ’94, DVM ’98 was appointed assistant editor for the Journal of the American Veterinary Medical Association (JAVMA) and the American Journal of Veterinary Research (AJVR), premier veterinary science journals published by the American Veterinary Medical Association.
From the stray-strewn streets of Trinidad and Tobago to cow-covered pastures of rural New York dairy farms, Miguella Paula-Ann Mark-Carew has journeyed far in her quest to understand and combat disease epidemics across the world. Ever since she came to Cornell’s College of Veterinary Medicine through a veterinary summer program when she was 17, Mark-Carew wanted to return as a full-time student. While attending Dartmouth College, she spent two respective summers conducting epidemiological research with Drs. Paul Bowser and Ted Clarke, and her positive experiences with Cornell faculty further sealed her aspiration. In 2007 she came to Cornell’s College of Veterinary Medicine as a doctoral student in the field of comparative biomedical sciences.
