ILLNESSOPEDIA

Intestinal cells may prompt Crohn's disease

A new study reveals that Crohn's disease may be a disorder of specialized intestinal cells, called Paneth cells. Researchers say this finding could provide new targets for treatment.

Results of the study, which was led by researchers from the University of Cambridge and Harvard University, were published in the journal Nature.

According to the researchers, Crohn's disease usually starts in early adulthood and is accompanied by cramping, diarrhea, weight loss, abscesses and fever.

Though the disease can go through periods of remission, it is a life-long disorder that is thought to develop in individuals who are genetically pre-disposed to the condition.

The researchers say Crohn's is thought to develop when these individuals encounter environmental factors, but these influencers are largely unknown.

Professor Arthur Kaser, from the University of Cambridge and a lead author on the paper, notes that the team's discovery of the role Paneth cells play in bowel inflammation "raises the possibility of entirely novel therapeutic approaches."

Prof. Kaser adds:

"If we are able to break down Crohn's disease into subsets by understanding the underlying mechanisms, which we have done here, we hope to develop much more targeted, effective treatments."

Paneth cells, shown here at the bottom of an intestinal crypt, play a role in bowel inflammation, researchers say.
Credit: Professor Arthur Kaser Genetic traits and environmental factors

Along with the discovery of the role Paneth cells play in Crohn's, the researchers identified another mechanism in the body that can lead to the disease.

Autophagy, which is the breakdown and reuse of cellular components in the body, can also lead to Crohn's disease, the researchers say.

Though autophagy was previously linked to the disorder - in that the process involves several key genes associated with Crohn's - how it played a role was unknown.

Previous studies speculated that the process led to the disease due to an inability to remove bacteria within the cells of the gut.

But the new research shows that autophagy keeps the inflammatory function of the unfolded protein response - a cellular stress response - in check. This is activated, say the researchers, when the endoplasmic reticulum (ER) - a network of tubes and flattened sacs that perform a number of functions within cells - is under stress.

The researchers say that ER stress is quite common in intestines of patients with Crohn's disease.

They hypothesize that autophagy may remove ER membranes that are presented as inflammatory by the build-up of misfolded proteins. This may be a result of genetic traits or environmental factors, they say.

Inducing autophagy

The team notes that their findings around how genes interact with ER stress genes and the environment is "an important aspect for our understanding of complex diseases, such as Crohn's disease."

By using drugs, such as rapamycin, the researchers speculated that targeting the interaction of ER stress and autophagy would induce the breakdown and reuse of cellular components.

Prof. Kaser says, however, that there is still work to be done:

"A similar drug to rapamycin had been used in a clinical trial for Crohn's disease but failed. However, we speculate that if it was studied in a specific subset of Crohn's, that the drug might actually prove effective."

According to the Crohn's & Colitis Foundation of America, Crohn's affects as many as 700,000 Americans. Though men and women are equally affected, the disease is more prevalent in individuals between the ages of 15 and 35.

The researchers say that although it was mostly a disease of the Western world in earlier decades, it is becoming more prevalent in other parts of the world, including China.