Rheumatoid Arthritis, can MAIT cells be our mates?

Rheumatoid arthritis (RA), an autoimmune disease that leads to stiff, deformed joints and often debilitating pain, affects 1.3 million adults in the United States. It results from the immune system attacking one’s own body, primarily at the joints and also other organs, such as the lung and the heart; however, these RA causing immune cells are not all villains. My preliminary results-oriented research suggests that a group of heroic T cells may actually protect us from arthritis. A SPARK grant will enable me to understand in-depth how these cells work during the disease and how to design new immunotherapy to help millions of RA patients worldwide.

For years, physicians have relied on an older generation of broadly immunosuppressive drugs with severe toxicity. Newer, biologic therapies directly counteract the overproduction of TNF, which is common in people suffering from RA. Since anti-TNF drugs suppress the immune system, they may also significantly increase the risk of infections. In addition, not all patients respond to or sustain a response to anti-TNFs over time, indicating an unmet need in RA therapy persists.

My work focuses on a population of unconventional T cells, Mucosal Associated Invariant T (MAIT) cells. These cells are highly abundant in the human immune system. While it takes days for conventional T cells to develop and become fully functional, MAIT cells are rapid responders and first-line defenders against invading pathogens. My work has identified a critical cellular factor to protect against arthritis, interferon gamma (IFNg). As its name suggests, this molecule can interfere with the immune cells, which drive the inflammation at the joints resulting in bone destruction and cartilage depletion. MAIT cells produce copious amount of IFNg within hours of activation. If I receive a SPARK award, I plan to take advantage of the new genetic tools to delete these cells in RA models and determine their functions in the disease. By using a novel small molecule that specifically activates MAIT cells to produce the RA protective IFNg, I will be able to understand the therapeutic effect of rallying this critical cell type in human patients.