"Translational Research in IBD" (Abreu et al)

As mentioned by Lian, Inflammatory Bowel Disease (IBD) is an overactive and uncontrolled immune response in the digestive tract. The article assigned this week, “Translational Research in Inflammatory Bowel Disease” (Abreu et. al) contains a good amount of information regarding the disease. The researchers identify that IBD is caused by a dysregulated mucosal immune response to a luminal antigen. Furthermore, people with IBD have an imbalance of T-helper effector cells and T regulatory cells being activated. The effector cells are identified as being responsible for producing the proinflammatory cytokines whereas the latter are responsible for producing the anti-inflammatory cytokines. The imbalance of these immune cells (more effector cells) results in inflammation and this leads to the protective layer of the gut being less effective, leaving the gut exposed and vulnerable.

The article notes that there are many causes and risk factors associated with IBD. A major risk factor includes genetic predisposition and therefore, people who have had occurrences of IBD in their family are more susceptible to the disease. The NOD2/CARD15 and OCTN1/2 genes and mutations of them are the primary genes associated with risk for IBD. The CARD15 gene is responsible for recognizing antigens and will release proinflammatory cytokines as a response. A mutation in this gene will lead to greater inflammatory responses. The OCTN genes function in carnatine transport across the membrane of epithelial cells in the GI. Mutations of OCTN lead to a greater amount of harmful antigens being transported across the membrane, which then warrants a greater immune response, which means more inflammation.

They also mention Toll-like Receptors (TLR) and Dendritic cells. The TLRs are expressed on cells in the GI and function in recognizing and binding antigenic ligands and after doing so, warrant an immune response. So basically, the TLRs contributes to a greater and more sensitive immune response. The Dendritic cells, they note, sample the contents in the lumen of the GI and upon sensing antigens/bacteria, will then signal T cells to either inhibit or activate an immune response.

It goes on by mentioning treatments, therapies, and ideas on how to treat IBD. They mention restoring the balance of all the cytokines and T cells involved in the immune response. This would help keep the inflammation in check. Another treatment is through the use of antibiotics/probiotics. The idea here is to repopulate the GI with the good or beneficial bacteria while ridding it of the bad bacteria.

They end off by mentioning the “IBD chip”. This chip would provide a personal and specific solution for the person with IBD. The chip would identify all of the genes and proteins expressed in that person’s mucosa and provide sort of a map on where and what to attack.

Abreu M, Sparrow M. Translational Research in Inflammatory Bowel Disease.