Researchers found that blocking iron accumulation in T cells with an antibody inhibited inflammatory cell activity.
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition characterized by the body’s immune system attacking its own healthy tissues. A person with SLE can experience a wide range of symptoms, including joint and muscle pain, inflammation, and fever. The condition can also cause organ damage.
Treating SLE can be challenging. Often, diagnosing the disease can take time, and treatment options are limited. Healthcare providers usually prescribe medications like hydroxychloroquine (Plaquenil), corticosteroids, or immunosuppressive agents to control the symptoms and prevent organ damage.
Now, a new study from scientists at Vanderbilt University Medical Center may have discovered a new approach to treating SLE.
For the research — published in Science Immunology — the scientists focused on T cells — a type of white blood cell that’s part of the immune system.
Based on previous research showing that iron appeared to be a common player in T cell dysfunction, and the T cells in people with lupus contained a high amount of iron, the researchers sought to clarify this further.
The team evaluated the iron-handling genes in T cells and discovered a transferrin receptor (CD71) that uptakes iron into the cells. They also found that this receptor was more highly expressed in the T cells of people with lupus and in mice genetically modified to be SLE-prone. This increased expression caused the T cells to take in too much iron.
When the scientists blocked CD71 with an antibody, T-cell iron levels decreased, reducing inflammatory T cell activity and enhancing the regulatory actions of T cells.
In addition, treating SLE-prone mice with the antibody reduced liver and kidney pathology. It also increased the production of IL-10 — an anti-inflammatory factor.
In T cells from people with lupus, blocking the receptor in lab experiments also enhanced production of IL-10.
“It was really surprising and exciting to find different effects of the transferrin receptor in different types of T cells,” co-author Kelsey Voss, PhD, said in a news release.
“If you’re trying to target an autoimmune disease by affecting T cell function, you want to inhibit inflammatory T cells but not harm regulatory T cells. That’s exactly what targeting the transferrin receptor did,” Voss added.