Shedding LIGHT on inflammation associated with inflammatory bowel disease
The intestinal immune system has to be carefully balanced to tolerate gut-resident bacteria and at the same time efficiently attack invading pathogens. Therefore, it is not surprising that imbalances of these regulatory mechanisms manifest in chronic inflammation of the intestinal tract. One of these disorders is called Inflammatory Bowel Disease (IBD) in which the mucosal immune system actively destroys the intestinal tissue.
In 2015, the Center for Disease Control and Prevention reported about 3 million Americans diagnosed with IBD which is an increase in the number of patients by 1 million since 1999. Medical treatment consists of anti-inflammatory therapeutics, but these are limited in efficacy and show unwanted side-effects. Given the lack of adequate treatment for IBD, it is important to understand the fundamental regulatory mechanisms of the intestinal immune system. The immune mediator LIGHT helps to activate immune cells and seems to play an important role in IBD as it was found to be present in high levels in the intestine of IBD patients. My study will focus on the examination of the influence of LIGHT on the pathology of ulcerative colitis, a chronic inflammation of the colonic mucosa, leading to diarrhea, rectal bleeding, severe abdominal pain and consistent weight loss in colitis patients.
Although LIGHT typically has been associated with promoting inflammation, surprisingly, we found that LIGHT-deficient mice treated with a colitis-inducing chemical showed a more severe disease progression, indicating a protective role for LIGHT and a possible treatment of colitis patients with LIGHT. But which cell type actually produces LIGHT? And what are its detailed effects when the colonic mucosa is chronically inflamed? As there are no reliable tools to easily detect LIGHT we have genetically modified mice to generate fluorescent LIGHT protein which can be visually tracked. In addition, we will generate mice with LIGHT deficiency in very distinct cell types to study its effects during colitis. Together, my studies will lead to a deeper understanding of chronic inflammatory conditions in IBD and towards finding a proper treatment for these patients.