Researchers have identified a molecular defect that triggers an abnormal immune response in lupus, a condition affecting more than 1.5 million people in the U.S. They suggest that correcting this defect could potentially reverse the disease.
Lupus, also known as systemic lupus erythematosus, has been a complex disease with unclear origins. It can lead to severe damage to various organs like the kidneys, brain, and heart. Current treatments for lupus are limited in their effectiveness and often come with side effects that weaken the immune system’s ability to fight infections.
Dr. Jaehyuk Choi from Northwestern University Feinberg School of Medicine and Dr. Deepak Rao from Harvard Medical School have highlighted a new approach to tackling lupus by addressing the root cause of the disease. They have identified an immune response imbalance in lupus patients and proposed specific mediators to correct this imbalance and suppress the autoimmune reaction that characterizes lupus.
In their upcoming publication in Nature, the scientists unveil a new pathway that contributes to lupus development. By studying changes in molecules present in the blood of lupus patients, they found that insufficient activation of the aryl hydrocarbon receptor (AHR) pathway leads to an excessive production of disease-promoting immune cells known as T peripheral helper cells, which stimulate the production of harmful autoantibodies.
To demonstrate the potential of their discovery for treatment, researchers reintroduced AHR-activating molecules to blood samples from lupus patients. This intervention seemed to transform the lupus-causing cells into Th22 cells, which are associated with wound healing, offering a promising remedy for the damage caused by the autoimmune response.
Dr. Choi emphasized the significance of this finding, suggesting that by activating the AHR pathway or limiting the excessive interferon levels in the blood, the number of disease-causing cells could be reduced, paving the way for a possible cure.
The team now aims to advance their research by exploring novel treatments for lupus patients, focusing on safe and effective ways to deliver these molecules for therapeutic purposes.
Other contributors to this research include authors from Northwestern University and Brigham and Women’s Hospital. The article, titled “Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus,” sheds light on the underlying mechanisms of lupus development.
This research was made possible with support from various grants from the National Institutes of Health (NIH) and contributions from organizations such as the Lupus Research Alliance, Burroughs Wellcome Fund, Bakewell Foundation, Leukemia and Lymphoma Society, and American Cancer Society.
