Autoimmune disorders, collectively characterized by immune system attack against the body’s own tissues, are the third most common disease type in humans (after cancer and heart disease). Besides LEMS, more than 100 autoimmune conditions have been identified, including type 1 diabetes, myasthenia gravis, and multiple sclerosis.
Though they are prevalent, most autoimmune disorders do not have a cure. With the overarching goal of designing treatments for such patients, a research team at Georgia State University will investigate the molecular mechanisms behind autoimmunity.
The immune system functions on two levels. The first level is an innate response activated quickly by foreign pathogens, such as parasites, bacteria, and viruses. Cells involved in the innate immune response do not need to be trained, but are deployed as needed to fight infection.
Over time, and in particular in the first three years after birth, exposure to various pathogens allows the B- and T-cells to more effectively distinguish between harmful agents and the body’s own cells later in life.
T-cells are produced in the thymus gland and can attack potential threats directly. If they become autoreactive despite the absence of a foreign threat, T-cells are supposed to be eliminated in the thymus in a process called central tolerance. Yet, as this mechanism is not 100% efficient, a secondary process called peripheral tolerance is set up to block autoreactive T-cells.
“The goal of this work is to better understand how the natural limitations of thymic selection predispose us to autoimmunity,” Leszek Ignatowicz, PhD, lead investigator of the study, said in a press release. “This research will provide a better understanding of cellular and molecular mechanisms driving autoimmunity and help to develop therapeutic strategies targeting autoreactive T cells that escaped central tolerance.”
With funding from the National Institutes of Health’s Institute of Allergy and Infectious Diseases, the team will use mouse models and a new RNA sequencing technology from 10x Genomics to better understand the mechanisms of central and peripheral tolerance. The project will span five years.
“From a clinical perspective, identification of dormant, autoreactive T cells is critically important for saving a new category of autoimmune patients with peripheral tolerance deliberately broken by regulatory T cells that silence treatments to enhance immunity to infection or cancer,” added Ignatowicz.
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