Scientists Uncover Potential Cause and Cure for Lupus

Lupus is an autoimmune disease that causes widespread inflammation and immune system dysfunction. Treatments have focused on controlling inflammation and suppressing the immune system, often resulting in toxic side effects. However, scientists at Northwestern Medicine and Brigham and Women’s Hospital have uncovered a major driver behind the immune dysfunction that defines lupus.

*Disclaimer:

The information provided in this article is for general informational purposes only and is not intended as medical advice. It should not be used as a substitute for professional diagnosis, treatment, or advice from a qualified healthcare provider. Reliance on any information provided in this article is solely at your own risk.

See a word you don't understand? Find it in our glossary.

Normally, T cells help control how the body responds to infection. A healthy immune system keeps these cells balanced so they do not become overactive. In people with lupus, however, this balance breaks down. A key pathway in T cells, controlled by the aryl hydrocarbon receptor (AHR), usually helps prevent the immune system from going overboard, but in lupus patients, it is not activated enough.

As a result, harmful immune cells called CXCL13-positive T cells grow immensely. These cells encourage the body to make autoantibodies, which attack healthy tissues. At the same time, helpful cells that normally promote healing, like Th22 cells, are reduced.

The second problem the researchers found involves a chemical signal in the immune system called interferons. In healthy people, interferons help fight viruses, but in lupus patients, there is excess interferon in their blood. The excess interferons block the AHR pathway even more, making it harder for the immune system to stay balanced.

Dr. Jaehyuk Choi, a researcher at Northwestern, explained that this creates a chain reaction. Too much interferon turns off, letting harmful immune cells grow out of control. His co-lead, Dr. Deepak Rao from Brigham and Women’s Hospital, said the team has found an imbalance that explains how lupus develops at the cellular level.

Once the scientists discovered these two issues, they tested ways to fix them. First, they added lab-made versions of AHR-activating molecules to the blood of lupus patients. These molecules successfully “reprogrammed” the harmful immune cells into safer, healing types. In addition to this, they also tried blocking the excess interferon in the blood. Eventually, the harmful T cells decreased, and healing cells returned. These changes show that the disease can be reversed if the immune system’s controls are reset correctly. The scientists are now working on ways to safely deliver these treatments to patients. While this will take time, the researchers believe that they are closer than ever to a real cure for lupus.

Most current treatments for lupus use drugs that suppress the immune system in general. While this can reduce inflammation, these drugs do not fix the root of the problem and often come with serious side effects. This new discovery gives a more targeted approach, as instead of shutting down the whole immune system, it focuses on correcting the specific immune defects that cause lupus. If future trials prove that these lab results work in real patients, this research could one day mean fewer medications, fewer hospital visits, and healthier, longer lives.

Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus | Nature

Researchers Identify a Disease-Causing Immune Cell Imbalance in Lupus | NIH​