Regulatory Immune Cell Diversity Tempers Autoimmunity in Rheumatoid Arthritis

Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence. Now, researchers at The Wistar Institute announce that it takes a diverse array of regulatory T cells (a specialized subset of white blood cells) to prevent the immune system from generating the tissue-specific inflammation that is a hallmark of the disease. Regulatory T cell diversity, the researchers say, provides a cumulative protective effect against rheumatoid arthritis. When that diversity is not present, it allows the immune system to attack joints.

The Wistar scientists presented their findings, developed in a mouse model of rheumatoid arthritis, in the May 1 issue of the Journal of Immunology. Defining the immune mechanisms involved in rheumatoid arthritis could point to new therapies for the disease.

“Our results show, surprisingly, that suppressing the immune response against a single target will not shut down the inflammatory response that causes rheumatoid arthritis,” said Andrew J. Caton, Ph.D., senior author and professor in The Wistar Institute Cancer Center’s Tumor Microenvironment and Metastasis program. “Instead, an array of inflammation-stimulating antigens may be involved in causing the disease, since our study shows that an array of regulatory T cells is required to temper the immune system’s attack on joints.”

Rheumatoid arthritis (RA) is an autoimmune disorder that occurs as the immune system attacks the synovium, the membrane that lines all the joints of the body. It is a common disorder that causes uncontrolled inflammation - resulting in pain and swelling - around the joints. It is thought that approximately one percent of the adult population, worldwide, suffers from rheumatoid arthritis. RA has shown to be exacerbated by drinking and smoking, and the disease can lead to an overall increased risk of death.

While the exact cause of RA is unknown, the Caton laboratory and others have shown that a variety of white blood cells called regulatory T cells (or Tregs) are a necessary component to either restrain (or encourage) the immune system’s inflammatory response. Tregs are activated as molecules on their surface membranes called T cell receptors interact with “friendly” or “self” molecules - a way for the immune system to recognize friend from foe. Mismanagement of these Tregs, which normally serve to restrain the immune system from over-reacting to healthy tissue, could then lead to runaway inflammation.

Rheumatoid arthritis is an inflammatory disease affecting about 1.3 million adults, and causes pain, swelling, stiffness, and loss of function in the joints. Several features make it different from other kinds of arthritis – such as generally occurring in a symmetrical pattern. This means that if one knee or hand is involved, the other one also is. The disease often affects the wrist joints and the finger joints closest to the hand, but it can also affect other parts of the body besides the joints. Rheumatoid arthritis (RA) occurs in all races and ethnic groups. The cause of the disease is not known, but it is believed to be an autoimmune disease (an illness that occurs when the body mistakenly detects its own tissue as foreign and attacks itself). Although the disease often begins in middle age and occurs with increased frequency in older people, children and young adults also develop it. Like some other forms of arthritis, rheumatoid arthritis occurs much more frequently in women than in men.