Fight Aging!

Autoimmune disorders are a major challenge for modern medicine; in most cases, there is little that can be done but suppress the immune system, a strategy that has serious side-effects. The fundamental causes of these conditions are poorly understood, and researchers lack good points of intervention to reprogram an aberrant immune system. The immune system is clearly very complex, and capable of malfunctions in countless different, equally complex ways. Given that, it is always good to see the research community making inroads towards the effective treatment of an autoimmune condition, and here systemic lupus erythematosus is the target. Interestingly, lupus presents quite differently depending on age of onset; late-onset lupus that emerges in old age exhibits both less severe symptoms and greater mortality than the condition in younger individuals.

The autoimmune disease systemic lupus erythematosus - known as lupus - affects more than 1.5 million people in the US. It can result in life-threatening damage to multiple organs including the kidneys, brain, and heart. The causes of this disease have long been unclear. Existing treatments often fail to control the disease and have unintended side effects of reducing the immune system's ability to fight infections. But now researchers have discovered a molecular defect that promotes the pathologic immune response in lupus and show that reversing this defect may potentially reverse the disease.

The scientists report a new pathway that drives disease in lupus. There are disease-associated changes in multiple molecules in the blood of patients with lupus. Ultimately, these changes lead to insufficient activation of a pathway controlled by the aryl hydrocarbon receptor (AHR), which regulates cells' response to environmental pollutants, bacteria, or metabolites, a substance created when the body breaks down food, drugs, chemicals or its own tissue. Insufficient activation of AHR results in too many immune cells that promote the production of disease-causing autoantibodies.

To show this discovery can be leveraged for treatments, the investigators returned the AHR-activating molecules to blood samples from lupus patients. This seemed to reprogram these lupus-causing cells into a type of cell that may promote wound healing from the damage caused by this autoimmune disease. "We found that if we either activate the AHR pathway with small molecule activators or limit the pathologically excessive interferon in the blood, we can reduce the number of these disease-causing cells. If these effects are durable, this may be a potential cure."

Link: https://news.northwestern.edu/stories/2024/july/lupus-immune-response-reversal/