A team of international researchers, led by the University of Plymouth, has unveiled a novel technique that could pave the way for discovering and developing new therapeutics for prevalent autoimmune diseases.
Reporting in Nature Biomedical Engineering, the researchers introduce the Secretion-Enabled Cell Ranking and Enrichment (SECRE) method, which promises to explain the altered release of inflammatory mediators called cytokines in immune cells—the root cause of conditions like lupus, rheumatoid arthritis, inflammatory bowel disease (IBD), and cell transplant failures.
Autoimmune diseases occur when the immune system mistakenly attacks healthy cells, leading to chronic inflammation and a range of debilitating symptoms. To address these diseases effectively, scientists need to identify the genetic regulators responsible for altered cytokine secretion, offering insights into potential therapeutic targets. The SECRE method, a result of a collaborative four-year effort between researchers in the U.K., United States, and Canada, proves to be a game-changer in this quest.
The SECRE technique involves sorting hundreds of millions of CRISPR-edited cells based on their secretion patterns, allowing scientists to pinpoint the genetic regulators of cytokine secretion in autoimmune conditions accurately. What sets SECRE apart is its integration of detailed profiles of approved and under-development treatments, enabling researchers to explore the reapplication of existing therapies in innovative ways.
“This is an incredibly novel approach that can potentially deliver huge benefits for patients, clinicians and the drug companies working to establish new treatments. It gives us the ability to sort large number of cells based on their secretion patterns and identify therapeutic targets that could be applied to help those with conditions for which there are currently few therapeutic options,” said Mahmoud Labib, a key contributor to the SECRE approach and Lecturer in the University of Plymouth’s Peninsula Medical School.
The researchers validated their approach by focusing on cells crucial to the development and severity of IBD, a condition affecting approximately seven million people worldwide with no known cure. By utilizing kinase inhibitors, including XMU-MP1, previously investigated for various medical conditions, the team observed promising results in mice with colitis resembling human IBD. The mice treated with XMU-MP1 exhibited reduced weight loss, milder colitis symptoms, and maintained normal colon appearance, suggesting the potential of this approach in controlling IBD.
The SECRE technique captures secreted cytokines on cell surfaces, labeling them with magnetic nanoparticles and sorting them within a microfluidic device created using advanced three-dimensional printing. This method enables rapid, high-throughput sorting of cells based on their secretion patterns, linking the functional signature of cells with their phenotype. According to the researchers, it also allows for the selective sorting of specific immune cell subsets based on surface markers and secretion-specific factors.
As the SECRE technique opens new doors in autoimmune disease research, its potential impact on treatment development could be substantial. While the findings regarding XMU-MP1 as a potential treatment for IBD are promising, extensive clinical trials are essential before it can be considered a viable therapeutic option. Nevertheless, the scientists believe that the SECRE method’s ability to accelerate the discovery of therapeutic targets holds promise for transforming the landscape of autoimmune disease treatment and, potentially, other complex conditions.