Inflammatory bowel disease (IBD) refers to a group of conditions that affect the intestinal tract. The main forms of IBD are Crohn's disease (which may affect any segment of the gastrointestinal tract) and ulcerative colitis (which mainly affects the large intestine or colon). These conditions are caused by abnormal regulation of the immune system, when the body doesn't react properly to bacteria present in the digestive tract. Typically, the body has adapted to live peacefully with these bacteria, many of which aide in the body's food digestion and other processes. For some individuals, however, the normal intestinal bacteria are treated as enemies to be attacked by the immune system, causing IBD.
There is no cure for these chronic conditions, and they have a severe impact on quality of life for the patient. Among many complications, Crohn's can cause stunted growth in children, and ulcerative colitis greatly increases the lifetime risk of contracting colon cancer.
Mitch Kronenberg, Ph.D., is studying IBD with an eye to determine, on a very fundamental level, how white blood cells contribute to this disease and how the body's T cells can help to stop it. In order to do this, his lab is examining several molecular interactions using animal model systems to find key molecules that cause IBD.
Kronenberg's lab has found that HVEM, a cytokine-receptor (proteins used to signal other cells) that was originally discovered by LIAI faculty Carl Ware, Ph.D, and collaborators, binds to BTLA and LIGHT, two other cytokines. When HVEM and LIGHT combine, the immune response, including inflammation, is increased. When HVEM and BTLA combine, in contrast, the immune response can be lessened. The lab's studies showed that the role of HVEM was primarily to promote the anti-inflammatory response in IBD by engaging BTLA, so now the lab is looking into ways to promote the presence of BTLA to battle the disease.
Klaus Ley, M.D., and his lab focus on the study of inflammation biology and how inflammation impacts Crohn's disease specifically. The Ley lab is looking at how cells move through the body, seeking ways that this knowledge can be applied to disease studies. In examining this, the lab has made discoveries of three molecules that can be blocked to effectively close off some of the pathways that cells use to move through the body. By blocking the alpha 4 integrin (a treatment that is now used clinically) in combination with another adhesion molecule, ICAM-1, the inflammation process related to IBD can be mitigated. Blocking the selctin ligand PSGL-1 also reduces inflammatory scores. It is hoped that future treatments based on these discoveries may lessen symptoms associated with Crohn's disease.
