Monday, October 20, 2014
New Target for Treating Autoimmune Disorders
The study published in Nature Immunology, shows that the receptor helps regulate intestinal inflammation in mice and that its activity can be manipulated, offering a potential new target for treating certain autoimmune disorders, such as Crohn’s disease and possibly multiple sclerosis (MS).
“We have a new way to regulate T-cell activation and potentially better control immune-mediated diseases,” said senior author Eyal Raz, MD, professor of medicine.
The receptor, called a TRPV1 channel, has a well-recognized role on nerve cells that help regulate body temperature and alert the brain to heat and pain. It is also sometimes called the capsaicin receptor because of its role in producing the sensation of heat from chili peppers.
The study is the first to show that these channels are also present on T-cells, where they are involved in gating the influx of calcium ions into cells – a process that is required for T-cell activation.
“Our study breaks current dogma in which certain ion channels called CRAC are the only players involved in calcium entry required for T-cell function,” said lead author Samel Bertin, a postdoctoral researcher in the Raz laboratory. “Understanding the physical structures that enable calcium influx is critical to understanding the body’s immune response.”
T-cells are targeted by the HIV virus and their destruction is why people with AIDS have compromised immune function. Certain vaccines also exploit T-cells by harnessing their ability to recognize antigens and trigger the production of antibodies, conferring disease resistance. Allergies, in contrast, may occur when T-cells recognize harmless substances and pathogenic.
In experiments with mice models, researchers were able to reduce colitis with a TRPV1-blocker, initially developed as a new pain killer. One of the promising discoveries is that colitis in mice could be treated with much lower doses that what is needed to dull pain. “This suggests we could potentially treat some autoimmune diseases with doses that would not affect people’s protective pain response,” Raz said.
Eighty-five percent of emerging disease is autoimmune. When triggered inappropriately, the immune system turn and attack the very body it is designed to protect. We give these diseases various names depending on what tissues or organs the immune system targets. In MS it is the nervous system, specifically the myelin sheath that covers the nerves. In Crohn’s Disease it’s the intestinal tract, Hashimoto’s Thyroiditis, the thyroid. The list goes on and on. However, many scientists believe all these conditions have a common trigger.
The GALT (gut associated lymphatic tissue) that follows the digestive tract continually samples substances in the gut, and then stimulates the thymus to influence T cell production. This creates a specific immune response to the offending substance in the digestive tract. If, however, the chemical makeup of that substance closely resembles some structure in the body, the immune system may attack that tissue or organ. This process is called molecular mimicry.
The drug(s) used in this study were all derivative of capsaicin. This herb has long been used to reduce pain. Its use to down regulate immune response is quite new and also quite promising. This is especially true since the dosage appears to much lower than that used to reduce pain. Capsaicin can irritate the digestive tract in traditional therapeutic doses.
THE BOTTOM LINE:
There are several autoimmune modulators that are effective in treating autoimmune disease – ginger, boswellia, echinacea, and now capsaicin. It is also vital to isolate the trigger from the digestive tract whether it is a viral infection or a food. Look closely at wheat (gluten), dairy, soy, and corn. They are very common triggers for autoimmune disease.
Source: University of California, San Diego School of Medicine -October 2, 2014