Karen Edelblum, PhD
I was diagnosed at the age of 13 with Crohn's disease. When receiving the news that you have a chronic illness, one of the most common thoughts you have is "why me?" From day one, I used my diagnosis as motivation to empower myself to help find a cure for IBD, not only for myself but for the thousands of other children, teenagers and young adults that suffer from this disease.
I believe strongly that basic science researchers should see how our work directly affects the lives of patients. For several years, I have hosted high school and college students with IBD as summer interns in my lab. While the student learns about biomedical research, the experience has also been invaluable for those working in my laboratory and reinforces our dedication to our work.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, affects 1.6 million Americans -- that's 1 in 200 people, including myself.
Although the exact cause of IBD remains unknown, faulty regulation of the immune system, the bacteria normally found in the intestine, along with genetic and environmental factors, all contribute to development of the disease. A single layer of cells called the epithelium, is the only barrier between the immune system and the food products and bacteria that pass through your intestine. Maintenance of this one cell layer-thick barrier is essential to prevent infection or leak of bacterial products, which would further activate the immune system.
Our laboratory has found that one group of immune cells called gamma delta intraepithelial lymphocytes (IEL) actively migrate among the cells that make up this barrier. This "border patrol" is required to prevent intestinal bacteria from invading epithelium and inducing inflammation. The patrolling behavior of gamma delta IELs changes when the epithelial cells recognize bacteria, and the gamma delta IEL is almost immediately attracted to an infected cell to prevent the bacteria from invading the tissue. Since many of the known genetic mutations associated with IBD are involved in the recognition and response to intestinal bacteria, we aim to better understand whether gamma delta IEL surveillance of the epithelium is altered in IBD patients. We hope that we can use the migratory behavior of these cells to reinforce the integrity of the intestinal barrier as a potential therapy to prevent disease relapse and maintain remission in IBD patients.
Why is this important?
The incidence of IBD is increasing both in developed and developing countries, which may be attributed to changes in diet and intestinal bacteria. Since this a chronic disease, patients may experience periods of active inflammation known as flares, undergo medical treatment and go into clinical remission, only to relapse later on. Studies have shown that IBD patients have a leaky barrier both during an active flare as well as prior to relapse of the disease. We want to determine whether gamma delta IEL surveillance could be used as a tool to limit this "leakiness" thus preventing an autoimmune response that would cause further injury and inflammation.
Current therapies focus on suppressing the immune system or stopping the continuous cycle of inflammation by inhibiting pro-inflammatory signals. Patient responsiveness to these treatments varies, which suggests that inhibition of one pro-inflammatory signal may only be sufficient to induce remission in a subset, but not all patients. We aim to find a therapy that will amplify the known protective role of gamma delta IELs to prevent the disease from progressing to the point in which anti-inflammatory medication is required.
Who will benefit?
This study focuses on patients with inflammatory bowel disease, both Crohn's disease and ulcerative colitis. Findings from these initial studies will give us further insight into how gamma delta IELs contribute to immune surveillance in response to intestinal bacteria, which may also have broader implications for other autoimmune diseases linked to the intestinal microbiome.