New Light on a New Technique That Can Pinpoint the Causes and Treatments of Autoimmune Diseases

Conditions such as lupus, rheumatoid arthritis and inflammatory bowel disease (IBD) — as well as failures within transplanted cells — are all caused by altered cytokine secretion of immune cells within the human body.

To find treatments for such diseases, experts need to identify the genetic regulators of the secretion so they can explore the most effective ways of inhibiting them.

An international team of researchers has developed a new method, referred to as Secretion-Enabled Cell Ranking and Enrichment (SECRE).

They have demonstrated the method is accurate in sorting hundreds of millions of CRISPR-edited cells based on their secretion patterns, and identifying the genetic regulators of cytokine secretion in an autoimmune condition.In addition to this, the method takes into account the detailed profiles of approved treatments, and those under development, to establish if therapies already in existence can be reapplied in new ways.

Writing in the study, the researchers detail how they have validated their approach on the cells known to play an essential role in the development and severity of IBD, and proved it has the potential of finding new ways of treating conditions that impact millions of people globally.

Inflammatory bowel disease (IBD) is a long-term health condition that has been estimated to affect around 7 million people worldwide. It is characterized by chronic inflammation of the digestive tract, which can result in severe tummy pain and diarrhea, and there is presently no known cure.

As part of work to validate their approach, the researchers examined the effect of several kinase inhibitors on CD4+ T cells, which are known to produce interferon gamma, a protein widely implicated in several autoimmune diseases including IBD. The inhibitors looked at included XMU-MP1, a small molecule that has previously been explored as a treatment for heart failure, hair loss and a number of other medical conditions.

In this instance, the researchers used XMU-MP1 to treat mice with a form of colitis that has a similar cell secretion profile to that found in humans with IBD. They found the mice experienced significantly less weight loss and reduced colitis symptoms, while their colons remained virtually normal in appearance and did not show any significant loss of intestinal stem cells.

Based on these findings, the researchers say their results suggest that using XMU-MP1 as a means to inhibit interferon gamma production in the gut may represent an ideal means to control IBD. They also say it provides a promising future strategy for the therapeutic molecular targeting of the condition, although extensive clinical trials would be required before it could be considered as a treatment.

Sources:

Mahmoud Labib, Zongjie Wang, Yunhye Kim, Sichun Lin, Abdalla Abdrabou, Hanie Yousefi, Pei-Ying Lo, Stéphane Angers, Edward H. Sargent, Shana O. Kelley. Identification of druggable regulators of cell secretion via a kinome-wide screen and high-throughput immunomagnetic cell sorting. Nature Biomedical Engineering, 2023; DOI: 10.1038/s41551-023-01135-w

Materials provided by University of Plymouth. Original written by Alan Williams. Note: Content may be edited for style and length.

University of Plymouth. “Scientists devise new technique that can pinpoint the causes and treatments of autoimmune diseases.” ScienceDaily. ScienceDaily, 27 November 2023. <www.sciencedaily.com/releases/2023/11/231127132253.htm>.

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