Autoimmune disorders are incredibly complex and can be very difficult to treat, in part because the cause of the disorder is often unclear. Scientists have now created a method that aims to pinpoint the cells that underlie diseases like inflammatory bowel disease (IBD), lupus, and rheumatoid arthritis. Thus study has suggested that aberrant immune cells that do not properly control the release of inflammatory signals called cytokines are to blame for these diseases. This new technique, called Secretion-Enabled Cell Ranking and Enrichment (SECRE), can sort through millions of cells to find the errors in cytokine secretion, and apply treatments more directly. The work has been reported in Nature Biomedical Engineering.
SECRE works by capturing cytokines that secreted on the surface of the cell, and tagging them with magnetic nanoparticles. They can then be sent through a microfluidic device that sorts them based on the cytokine secretion pattern. The genotype and phenotype of the cells can be linked to identify specific cell subsets that have specific secretion characteristics.
The researchers validated this method by generating huge amounts of cells that were modified with the CRISPR gene editing tool. Cells that are known to be related to IBD development and severity were sorted out, and the investigators are hopeful that this will improve treatment options for patients.
This is an "incredibly novel" new approach provides researchers with the ability to analyze cells based on their secretion patterns to find treatment targets, particularly for those who have few options, noted Dr. Mahmoud Labib, Lecturer in the University of Plymouth's Peninsula Medical School. This method might also be expanded for use in some cancer treatments, added Labib.
CD4+ T cells release a cytokine called interferon gamma, and these cells have been associated with a variety of autoimmune diseases. The investigators assessed the impact of kinase inhibitors on these cells, such as XMU-MP1, which has been studied as a possible treatment for several medical conditions including heart failure.
When a mouse model of colitis was given XMU-MP1, colitis symptoms were relieved, and they lost less weight than untreated mice. The colons of treated mice showed little sign of disease, and there was no significant loss of stem cells in their intestines. The scientists suggested that XMU-MP1 could work to limit interferon gamma production in the gut, and reduce IBD symptoms. More work will be needed to confirm these results in humans before the therapy can be tested in people, however.
Sources: University of Plymouth, Nature Biomedical Technology
