A new study has shed light on a poorly understood therapy developed to treat individuals with autoimmune diseases. The researchers not only revealed the molecular mechanisms behind the therapy, but also identified an optimal strategy that will reduce treatment-associated risks and result in long-term modulation of rogue immune system cells. The work has been published in Nature Communications.

Autoimmune diseases—such as multiple sclerosis, type 1 diabetes and rheumatoid arthritis—are chronic inflammatory conditions that result from the body’s immune cells inappropriately attacking healthy tissues. This happens because the immune system is unable to distinguish between your own tissue and potentially harmful substances.

Scientists have made progress in developing treatments for these diseases in recent years, but in order to be successful the treatments need to be long-lasting and should not affect normal immune function. A specific type of therapy called antigen-specific immunotherapy aims to tick these boxes and has been shown to work in some trials.

The therapy involves administering increasing doses of the molecules that the body normally attacks, which gradually builds up a tolerance to them. However, the best dose to create safe, long-term protection was unknown. Furthermore, scientists did not understand the underlying mechanisms that led to this tolerance. Now, a new study conducted by researchers at the University of Bristol has shed light on both of these areas, which will hopefully lead to more effective treatments.

For the current study, the researchers looked at a type of white blood cell called a CD4+ T cell—one of the most important players in autoimmunity. These cells usually help fight infection, but in individuals with autoimmune diseases they drive the immune response that results in inflammation.

The researchers administered increasing amounts of protein fragments that are normally the target for attack and looked at which genes were switched on inside the CD4 cells at different stages. They found that as the dose escalated, genes that positively regulate inflammation and cell cycle pathways were switched off. This caused the cells to convert from aggressive cells into protective cells. Furthermore, they identified the genes that characterize these CD4 cells.

From this, the researchers were able to develop an optimal dose escalation strategy that efficiently reinstates self-tolerance. This means that instead of attacking self tissues, the immune system gradually begins to ignore them. Importantly, this is achieved without the need for immunosuppressive drugs that have undesirable side effects, such as leaving the individual susceptible to infections and tumors.

“Insight into the molecular basis of antigen-specific immunotherapy opens up exciting new opportunities to enhance the selectivity of the approach while providing valuable markers with which to measure effective treatment,” lead researcher David Wraith said in a news release. “These findings have important implications for the many patients suffering from autoimmune conditions that are currently difficult to treat.”

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