Math model of colon inflammation singles out dangerous immune cells

Jul 22, 2010

Scientists at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have constructed a mathematical and computational model of inflammatory bowel disease that allows researchers to simulate the cellular and molecular changes underlying chronic inflammation in humans. The model allows scientists to explore different interactions of cells in the immune system, check how these cells are linked to inflammation in the colon, and identify intervention points to perhaps stop the disease in its tracks. The work appears in the Journal of Theoretical Biology.

More than 1 million people are affected by inflammatory bowel disease in North America alone and direct healthcare expenses for inflammatory bowel disease in the United States are estimated at more than $15 billion annually. What the scientists have been able to do is construct a set of mathematical equations that describe the movement of different cells in the immune system and how these cells interact with different bacteria that can trigger disease in the colon.

Said Josep Bassaganya-Riera, associate professor at VBI, "In collaboration with the Network Dynamics and Simulation Science Laboratory at VBI, researchers in the Nutritional Immunology and Molecular Medicine group have developed a model of inflammation that allows us to investigate in silico the immunological changes that occur when inflammatory bowel disease takes hold of otherwise healthy gastrointestinal tissue."

Inflammatory bowel disease starts when the gut initiates an abnormal to some of the one hundred trillion or so bacteria that come into contact with the colon of the human body. In some cases, this response can lead to inflammatory lesions and ulcerations in the cells lining the colon through which bacteria can invade the tissue. This invasion can lead to recurring inflammation, diarrhea, rectal bleeding, and malnutrition, the tell-tale symptoms of inflammatory bowel disease and infections with some gastroenteric pathogens.

Said Stephen Eubank, deputy director of the Network Dynamics and Simulation Science Laboratory at VBI and one of the authors on the paper, "One thing we are trying to understand with this research is how your immune system lives in peace with the commensal, peace-loving bacteria, yet can still mount a rapid, controlled defense against unfriendly bacteria. We are also interested in what happens when parts of the immune system do not behave as expected, for example when otherwise friendly immune cells attack healthy tissue." Remarked Eubank: "The described in this paper allows scientists to examine these types of events in considerable detail but we are already working on a next-generation model that will allow us to take an even bigger step. Our goal is to develop an agent-based model in a petascale computing environment that will be able to represent hundreds of millions of cells involved in this type of immune response."

Previous studies have shown that in healthy individuals the detrimental immune response is avoided by the presence of regulatory immune cells that inhibit the inflammatory pathway. Added Bassaganya-Riera, "Our model allows researchers to identify those components of the inflammatory pathway that allow regulatory mechanisms to be overridden and immune-mediated disease to proceed."

The mathematical and computational approach of the scientists has already revealed one of the weak links in the complex network of interactions. Said Katherine Wendelsdorf, a graduate student in the Network Dynamics and Simulation Science Laboratory at VBI and lead author of the paper, "Our math analyses revealed a specific type of immune cell, a pro-inflammatory macrophage, to be one of the main culprits for unregulated inflammation in ."

When conditions were simulated in which M1 or classically activated macrophages were removed from the site of infection, a drastic decrease in the inflammatory response linked to disease was observed in the simulations. This observation suggests that M1 macrophages are key targets for intervention strategies to fight mucosal inflammation.

Said Bassaganya-Riera, "Modeling approaches cannot replace experimentation but they can provide a framework for organizing existing data, generating novel mechanistic hypotheses and deciding where to focus key validation experiments. Future efforts in our group will focus on modeling immunity to enteric pathogens."

Explore further: A better understanding of piglet immune response to intestinal parasites

More information: Wendelsdorf K, Bassaganya-Riera J, Hontecillas R, Eubank S (2010) Model of colonic inflammation: Immune modulatory mechanisms in inflammatory bowel disease Journal of Theoretical Biology 264(4): 1225-1239.

add to favorites email to friend print save as pdf

Related Stories

First step to new therapy for chronic bowel disease

Jul 06, 2010

Scientists associated with VIB (Flanders Institute for Biotechnology) and Ghent University (UGent) have discovered that A20 protein plays an important protective role in diseases associated with chronic bowel inflammation. ...

2 immune-system proteins linked to colitis-associated cancer

Feb 02, 2009

Recent research from the laboratory of Michael Karin, PhD, at the University of California, San Diego School of Medicine - the first researcher to demonstrate a molecular link between inflammation and cancer - has identified ...

Bugs in the gut trigger production of important immune cells

Oct 15, 2008

A new study reveals that specific types of bacteria in the intestine trigger the generation of pro-inflammatory immune cells, a finding that could eventually lead to novel treatments for inflammatory bowel disease and other ...

Recommended for you

Dwindling wind may tip predator-prey balance

5 hours ago

Bent and tossed by the wind, a field of soybean plants presents a challenge for an Asian lady beetle on the hunt for aphids. But what if the air—and the soybeans—were still?

Environmental pollutants make worms susceptible to cold

10 hours ago

Some pollutants are more harmful in a cold climate than in a hot, because they affect the temperature sensitivity of certain organisms. Now researchers from Danish universities have demonstrated how this ...

Research helps steer mites from bees

12 hours ago

A Simon Fraser University chemistry professor has found a way to sway mites from their damaging effects on bees that care and feed the all-important queen bee.

User comments : 0