How do gut pathologies arise and why is our immune system unable to prevent it? I am happy to say that our lab at The University of Chicago believes that the answer is the abnormal activation of an ancient pathway and its effector protein Beta-Catenin.
The Wnt/Beta-Catenin pathway is highly evolutionarily conserved and has roles in everything from embryonic development to cel-cell communication. There's a good chance that if you look at any human cancers, the Wnt/Beta-Catenin pathway is negatively affected.
Our research, spearheaded by lead author Dr. Shilpa Keerthivasan, has shown that in patients with colitis or colon cancer, Beta-Catenin is highly expressed compared to healthy patients.
Incredibly, she worked out on the cellular level that this activation corrupts the function of T-cells that regulate the immune system (Tregs). Instead of suppressing the activation of the immune system, these Tregs instead cause inflammation. What makes matters worse is that the other T cells that become activated can no longer be shut down. In the gut, activation of T cells is fairly common because T cells are constantly coming in contact with bacteria (as can be seen in the image below). The gut has the highest concentration of immune cells so you can imagine that improper activation of these cells can have catastrophic effects. This is why it's really crucial to have normally functioning Tregs. Once these Tregs become corrupted, activation of the immune system spirals out of control. In fact, if you transfer these corrupted Tregs to healthy mice, they also develop gut inflammation.
These findings are huge because now we have a good idea as to how colitis and colon cancer can seemingly develop sporadically. The next step is finding out what activates this pathway in people. Don't worry, we're on it!
The press release (less jargon) can be found here: http://www.eurekalert.org/pub_releases/2014-02/uocm-bat022414.php
The article can be found here (unfortunately, it's behind a paywall) http://stm.sciencemag.org/content/6/225/225ra28.short?rss=1
Photo credits: http://scicasts.com/disease-processes/6438-location-in-the-body-where-immune-cells-reach-maturity-is-important-for-their-later-function/ #scienceeveryday