Researchers at Case Western Reserve University School of Medicine have received a five-year renewal program project grant totaling $9.7 million to study how the immune system can lead to the development of Crohn’s disease, which may put researchers on the right track for developing a cure for the disease.
The grant has been awarded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institute of Health.
Although it was previously thought that excess stress and diet could lead to the development of Crohn’s disease, researchers now believe that while these may worsen the symptoms, they are not a direct cause of the disease, and a combination of genetics and a faulty immune system are the current leading candidates as causes of Crohn’s.
Now, a team led by Dr. Fabio Cominelli, MD, PhD, a professor in the departments of medicine and pathology at Case Western Reserve University School of Medicine and director of Case’s Digestive Health Research Institute is hoping to find out why mice, in which gut inflammation occurs spontaneously, seem to be predisposed to develop Crohn’s disease. In the future, they expect to replicate their findings in humans, which may lead to the development of novel therapies for patients with the disease.
Previous work by Cominelli and his colleagues had suggested that Crohn’s disease may be a result of an abnormal immune response to an unknown antigen in a person that is genetically susceptible. An antigen is a molecule that is recognized by the immune cells as foreign, inducing an immune response.
In fact, they found that mice with ileitis, which is an inflammation in the lower parts of the small intestine, had decreased numbers of immune cells that are controlled by the NOD2 gene, and as a result, the mice’s immune system was not removing harmful antigens adequately.
“Before and during the first five-year project, my colleagues and I provided evidence of the importance of innate immunity and the role of what’s called the NOD2 gene,” Cominelli said in a press release. “This gene supplies instructions for making a protein that helps protect the body against foreign invaders in a disease called ileitis.”
Given that Crohn’s disease is an inflammation of both the small and large intestines, understanding how the immune system functions in ileitis may provide insights on how it works in Crohn’s disease.
The renewal project, which will continue to be led by Cominelli, will comprise three component projects, headed by Cominelli; Dr. Derek Abbott, MD, PhD, associate professor of pathology and medicine; and Theresa Pizarro, PhD, professor of pathology and medicine. This multidisciplinary project aims to study the NOD2 gene, as well as the NOD1, interleukin (IL)-1, and IL-33, all of which are known to participate in the body’s immune responses. The researchers expect to understand how these molecules impact the bacterial composition of the intestine, known as the gut microbiome.