spotlight on dr dougherty

Researchers on the Path to a Cure – Spotlight on Dr. Edward Doherty

Why is my immune system attacking my joints? What is the cause? If you have rheumatoid arthritis (RA), this is something you have probably wondered at some point. It’s something Dr. Edward Doherty has wondered as well, and is currently studying. Dr. Doherty and his co-investigator, Dr. Pathricia Tilstam are studying key cells that drive inflammation in their 2-year Arthritis Foundation-funded project, “MIF/CD74 signaling as a new candidate for immunotherapy of rheumatoid arthritis”. With autoimmune disorders like RA, something triggers the immune system to malfunction and attack healthy cells, causing inflammation and disease. Dr. Doherty and Dr. Tilstam are looking for some of the triggers to help develop more effective treatments to stop progression and joint destruction.

Dr. Doherty has a background in immunology and has always been interested in the autoimmune process. His late grandmother is a large part of his inspiration. For years, Dr. Doherty watched rheumatoid arthritis wreak havoc on her health. While studying medicine she would ask him “Why don’t you work on a cure for my arthritis?” This fueled his fascination with autoimmunity which has ultimately led to this project.

Dr. Doherty and Dr. Tilstam previously identified a relationship between certain types of cells in the immune system and severe erosive RA. The adaptive immune system works through the action of several different types of cells, including T cell subsets, B cells, and macrophages.

T cells, are a type of white blood cell that respond to infection. Once activated, T cells rapidly divide and fight infections. Macrophages are formed in response to infection and they engulf and digest damaged cells and microbes that cause infection (like bacteria and viruses) so that new, healthier cells can grow and replace old cells.

So, how do these things differ in a joint with RA? Researchers have found two things that appear in RA joints that aren’t seen in healthy joints: (1) high amounts of a protein, called macrophage migration inhibitory factor (MIF), and (2) specialized T cells (called CD74+ T cells). The CD74+ T cells are different because they have MIF receptors. Most T cells don’t have MIF receptors. Dr. Doherty feels the presence of both the CD74+ T cells and MIF is important to the development of RA.

In this disease, MIF acts as a driver for inflammation. Dr. Doherty believes it can trigger the CD74 T cells, causing an acute immune response that signals increased activation of macrophages, causing continued inflammation and joint damage. Dr. Doherty and his team are using mice to study this problem. They are trying to see if removing MIF will prevent or reduce joint inflammation.

While Dr. Doherty’s current project is geared towards inflammation caused by RA, he hopes  the things learned will translate to OA and other forms of arthritis. He and his team are interested in looking at the role of T cells in OA and other rheumatic disease joint degradation in the future.

Dr. Doherty and Dr. Tilstam are both postdoctoral associates in medicine (rheumatology) at the Yale School of Medicine.

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