For Some Crohn's Patients, This Dysfunctional Gene Could Be the Cause

Throughout the years, research has suggested that genetics play a role in the development of Crohn’s disease. In fact, researchers have found a link between Crohn’s disease and genetic mutations located on chromosomes 5 and 10. It appears that these mutations may increase an individual’s risk of developing the disease. It has also been found that 5-22% of individuals with Crohn’s disease have a first-degree relative with the disease. The reason why one individual may develop this disease while another may not is thought to be a result of the individual’s genetic makeup.

In other words, anyone who develops Crohn’s disease has some sort of a defective gene or genes that cause their immune system to respond in an abnormal way and trigger active inflammatory cells to the intestine. For this reason, a majority of current treatments for Crohn’s disease focus on suppressing the overactive immune response of the body.

Genetic modifications affect the presence of bacteria within the gastrointestinal tract. Any changes to these bacteria can harm the intestinal cells’ ability to respond normally. If the intestinal cells fail to respond normally to these changes, they can trigger inflammation associated with Crohn’s disease.

A new study hints at causes of Crohn’s

According to a recent study conducted by researchers at The Scripps Research Institute (TSRI) and published in the journal Immunity, circulating immune cells adapt to various tissues, which are much like various environments within the body. Failure to adapt to these tissues can lead to Crohn’s disease.

The researchers were hopeful in understanding exactly how immune cells adapt when they enter various tissues, in an attempt to design improved and more specific medications. “We need therapeutic strategies that specifically target chronic inflammation in the gut, skin or other tissues, instead of just generally suppressing the entire immune system,” said Mark Sundrud, biologist. Sundrud and his team worked on defining functions and features of TH17 cells, which are a subgroup of immune cells that move throughout the body. TH17 cells help to protect several tissues with the body for getting infected, but they also help to promote the occurrence of inflammatory conditions, such as Crohn’s disease. The researchers wondered how and if the TH17 cells used different tools to behave normally in different environments. They figured that much like how some genes are beneficial to the lungs, others could be beneficial to the gastrointestinal tract.  

Why was this study conducted?

This study was conducted based on previous data gathered from the Sundrud lab, which found that when TH17 cells entered the intestine, they increased the expression of a gene known as MDR1. Since MDR1 is a gene known to carry chemotherapeutic drugs out of cancerous cells, what role would it play on the immune cells within the gastrointestinal tract? The liver produces bile acids after eating in order to facilitate digestion. As food particles move within the gastrointestinal tract, the bile acids are reabsorbed once they reach the ileum. For this reason, the researchers uncovered that MDR1 is responsible for protecting TH17 cells from bile acids within the gastrointestinal tract. “T cells only see high levels of bile acids in the ileum. They know this, and they adapt once they get there,” said Sundrud.

Read on to learn more about the results of this study and what they mean for Crohn's disease.