Newly Discovered 'Backup' Immune System Could Help Doctors Improve Crohn's Treatment

When attacked with a toxic pathogen, Crohn’s disease patients experience a failure in the main immune system response, as well as a newly discovered “backup” system in the cells lining the gastrointestinal tract. That’s the latest finding from the immunology team at the University of Texas Southwestern.

Crohn’s disease, a chronic inflammation of the gastrointestinal tract, limits or reduces the body’s waste cleanup system, known as autophagy. The research conducted by the UT Southwestern team is the first known discovery of an additional avenue that is failing — and could be targeted for treatment — in people with Crohn’s disease.

“This is the first example of this alternative pathway being used in immune defense in any kind of animal,” said Dr. Lora Hooper, Chair of Immunology at UT Southwestern and leader of the lab that did the research.

Those suffering from Crohn’s can experience a failure in their immune systems as well as the newly discovered backup system present in the cells of the gastrointestinal tract lining. A new, secondary pathway was discovered by studying the disease in mice. The mice with a normal system were compared to the mice that were bred having the same genetic mutation most commonly found in Crohn’s patients. The secondary pathway was discovered in the cells lining the intestine, which are normally known to produce a certain small, antibacterial compound that is on the surface of the cells to create a type of barrier against pathogens. The lining is very important, and the bacteria there are necessary for the better digestion of food, but they can also cause ailments if they start to attack the tissues. Autophagy is considered to be the housekeeping system of the body: whenever there is waste produced or if there are proteins being used, the process of autophagy tries to clean through the cells as well as the waste to determine what needs to be recycled and what has to be removed. In the case of Crohn’s patients, the process of autophagy is very important for its role in inflammation as well as cytokine production. The process of autophagy is known to recycle the activated proteins to limit cytokines, which are overactive in Crohn’s disease.

Cytokines are essentially helpful proteins present in the body that aid in the regulation of both the immune and inflammation responses. Whenever the body is under threat from infection, cytokines are produced to send out signals for help to other cells. These are also known to be helpful in clotting as well as spurring on the immune system so as to adapt to any future threats. The process of autophagy is singled out first by losing nutrients, danger signals, and infection. Those who suffer from Crohn’s disease are known to have a mutation of the NOD2 and the ATG16L1 genes.

Crohn’s disease is often linked to genetics, the immune system, and environmental factors.

• Genetic factors: If an individual has an identical twin with Crohn’s, they have a 70 percent chance of developing the disease as well. Those with Crohn’s are also known to be twice as likely to have the gene mutation than those who do not have it. But not all individuals with the mutation will develop IBD such as Crohn’s disease.
• Environment: It is still unclear if environmental factors can cause Crohn’s, but there has been strong evidence to suggest that such factors can cause irritation if the disease is already present. A few environmental factors are smoking, viruses, food, and bacteria. The environmental factors are known to trigger the inflammation response, which can lead to painful symptoms.