Researchers have pinpointed a vital protein as a promising therapeutic target to prevent the immune system from erroneously attacking the body. This discovery brings new possibilities for addressing autoimmune diseases and allergies. The study highlights that by targeting the protein Apex1 with chemical inhibitors—either to deactivate it or eliminate it entirely—it may serve as an effective strategy to prevent immune-related disorders.
Scientists at Houston Methodist have identified a crucial protein that might help halt the immune system from mistakenly attacking the body, presenting new possibilities for the treatment of autoimmune diseases and allergies.
The research article titled “Apex1 safeguards genomic stability to ensure a cytopathic T cell fate in autoimmune disease models” was recently published in the Journal of Clinical Investigation. The study was co-authored by Xian C. Li, M.D., Ph.D., who heads the Immunobiology & Transplant Science Center at the Houston Methodist Research Institute, along with Zhiqiang Zhang, Ph.D., an associate professor specializing in transplant immunology.
In this examination, the team found that a protein known as Apex1 plays a protective role in the DNA of proliferating immune cells, enabling them to transform into “killer” T cells. If these T cells mistakenly attack the body, it can lead to autoimmune diseases and allergies. The researchers emphasized the critical role of the Apex1 protein in the harmful autoimmune response. By targeting this protein with chemical inhibitors to either switch it off or completely remove it, they demonstrated that it could be a powerful method to prevent immune-mediated disorders. Without Apex1, T cells lose the ability to inflict the damage associated with autoimmune diseases and allergic reactions.
“We were taken aback by how effectively blocking just that one Apex1 molecule could suppress various autoimmune diseases, not only preventing them but also treating them once they had already developed,” Li remarked. “Another surprising discovery was the significant death of harmful T cells following the inhibition of Apex1.”
The research team explored a variety of disease models, finding promising results particularly in lupus and multiple sclerosis. They deleted the Apex1 gene in mouse models predisposed to a lupus-like condition—where the immune system attacks its own tissues. The mice lacking the Apex1 gene did not show lupus symptoms such as protein in their urine, kidney damage, or the accumulation of harmful immune cells in their kidneys, nor did they produce damaging autoantibodies, resulting in prolonged healthy lives. In contrast, the control group, which displayed those lupus symptoms, succumbed by 24 weeks. The absence of the Apex1 gene appeared to stop the lupus-like disease by regulating harmful immune cells, indicating that Apex1 is crucial for the proper function of immune cells and could be a significant target for treating lupus and other autoimmune diseases.
“For individuals dealing with lupus, multiple sclerosis, or allergies where destructive T cells are present, targeting Apex1 may be the most effective approach to cure these diseases, as it leads to the elimination of harmful T cells through cell death,” Li stated. “We provided evidence of this concept in our paper using chemical inhibitors of Apex1.”
Li pointed out that their findings differ from previous approaches because they demonstrate that targeting Apex1 affects only the T cells that are currently multiplying after being activated by triggers, such as those seen in autoimmune diseases like lupus when these immune cells encounter specific antigens they recognize as threats. This reveals a remarkable specificity, suggesting that this potential treatment could be very accurate, minimizing unwanted side effects compared to other therapies.
Looking ahead, the researchers plan to develop chemical compounds designed specifically to target Apex1 and conduct further tests in additional models and clinical trials.
“In the next phase of our studies, we aim to test Apex1 inhibitors and Apex1 gene knockout in organ transplant models, where T cell-dependent graft rejection is a concern,” Li said. “Our goal is to create new protocols and enhance therapies for transplant patients to ensure the long-term success of transplant survival.”
