SRxA’s Word on Health was very excited to learn of some amazing new research coming out of UC San Francisco. Scientists there have identified a new way to manipulate the immune system and keep it from attacking the body’s own molecules in autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis.
More than 100 different autoimmune diseases have been discovered and they disproportionately affect women. Of the 50 million Americans living and coping with autoimmune disease more than 75% are women. Autoimmune diseases are one of the top 10 leading causes of death of women under the age of 65 and are responsible for more than $100 billion in direct health care costs annually. Crohn’s disease, ulcerative colitis, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis and scleroderma by themselves account for > $50 billion.
But now, researchers, led by immunologist Mark Anderson, MD, PhD, a professor with the UCSF Diabetes Center, have discovered a type of immune cell called an extrathymic Aire-expressing cell (eTAC), which puts a damper on immune responses. eTAC’s are a type of dendritic cell – which make up less than 3% of the cells in the immune system. And, eTAC cells themselves account for a small fraction of all dendritic cells. eTACs reside in lymph nodes and spleen in both humans and mice.
In this study, Anderson’s team determined that eTAC’s can counteract the overactive immune response in autoimmune diseases and, in a mouse model of diabetes, can be manipulated to stop the destruction of the pancreas.
By displaying “self” molecules to T cells that target them, and permanently turning off these T cells, eTACs help the immune system tolerate the molecules naturally present within us. “The mouse model we are working with involves using T cells that normally attack the islet cells of the pancreas, specifically by recognizing a molecule called chromagranin A that is present on islet cells,” Anderson said. “But if the eTACs can get to the T cells first and display chromagranin A, they can prevent T cells from attacking the islets.”
Anderson aims to exploit eTACs therapeutically by finding out how to grow them in large numbers outside the body. “We need to figure out how to grow a lot of these cells, to load them up with whatever molecule it is that we want to induce tolerance to, and then to load them back into a patient,” he said. “Such a strategy could help selectively shut down an unwanted immune response, such as the anti-islet immune response in type 1 diabetes.”
Dendritic cells work with T cells a bit like a sheriff working with a bloodhound. But instead of presenting an article of clothing, dendritic cells present a specific molecule. If the molecule displayed by the dendritic cell matches the one the T cell was born to target, then that T cell would be activated to expand its numbers and to attack cells or tissues where the molecule is present.
When the interaction is between eTACs and T cells, however, the targeted T cell instead is turned off forever, and never seeks its molecular prey.
Given that the prevalence and incidence of and type 1 diabetes and other autoimmune diseases, such as Crohn’s, lupus and celiac disease are on the rise, this new research is extremely important, both from a public health and economic perspective. With as many as three million Americans having type one diabetes and the incidence growing by more than 3% per year a cure is desperately needed.