Scientists have designed a new protein to treat autoimmune diseases

Scientists have designed a new protein to treat autoimmune diseases

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Today, it is estimated that 5 to 8% of the world’s population is affected by autoimmune diseases, pathologies in which the immune system attacks the body’s healthy tissues. Currently, for most of these diseases, there are only ways to treat the symptoms. Recently, researchers have designed a protein that can activate and increase the number of regulatory immune cells capable of preventing the onset of autoimmune diseases in mice. Although clinical application is still a long way off, this discovery opens a new path in therapeutic research.

Generally speaking, if infectious agents such as bacteria or viruses enter the body, the immune cells kill or overcome them, clearing the infection. This is called an immune response.

An autoimmune disease occurs when the immune system attacks the body’s own healthy organs and tissues instead of attacking bacteria, viruses, or other sources of infection. There are more than 80 types of autoimmune diseases that affect a wide variety of body parts.

Some are well known, such as type 1 diabetes, multiple sclerosis, lupus, and rheumatoid arthritis, while others are rare and difficult to diagnose. With uncommon autoimmune diseases, patients can suffer for years before receiving a proper diagnosis. Most of these diseases are incurable. Some require lifelong treatment to relieve symptoms.

According to’Pastoral Institutethey affect approximately 5 million people in France and constitute the third group of diseases in terms of morbidity and mortality in industrialized countries after cancer and cardiovascular diseases.

Doctors do not know why autoimmune diseases occur in the first place or why women are affected more than men. However, studies suggest that these diseases likely result from interactions between genetic and environmental factors.

On the one hand, characteristics of gender and ethnic origin are associated with a certain probability of developing an autoimmune disease. On the other hand, an environmental factor such as infection, stress, medication, diet or even ultraviolet radiation can play a role in the development of these pathologies.

In this context, a team of engineers at Johns Hopkins attempted to develop a cellular-level means of preventing and treating autoimmune diseases based on regulatory cells. They designed a protein that activates and increases the number of special regulatory T cells (called Tregs) that help prevent such disorders. Their results are published in a journal Cell messages.

Regulatory T cells, the key to autoimmune diseases?

Regulatory T cells, or Tregs, are white blood cells that regulate the immune system. They inhibit essential components of adaptive and innate immune responses, such as T cell proliferation and cytokine production. This function would be modulated by interleukin-2 (IL-2). Natural Tregs are indeed characterized by expressing both the T-cell co-receptor CD4 and CD25, which is a component of the IL-2 receptor.

Jamie Spangler, an assistant professor in the Department of Chemical and Biomolecular Engineering and Biomedical Engineering and a member of the research team, says communicated : ” Tregs are essential for keeping our immune system in balance, and when they fail, humans can develop autoimmune diseases. “.

Incidentally, IL-2 first received FDA approval as a high-dose pro-inflammatory agent to treat metastatic cancers. In contrast, low doses of IL-2 have already been used to treat some autoimmune diseases such as diabetes and ulcerative colitis, as well as transplant rejection. However, low-dose IL-2 strategies are limited by the dangerous effects of off-target immune cell activation and the short serum half-life of IL-2.

Recent work has shown that complexes containing human IL-2 (hIL-2) and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over other immune cells.

A protein made to control the immune system

Therefore, the authors created a single-chain protein called immunocytokine F5111 (IC) that fuses the cytokine interleukin-2 and the anticytokine antibody F5111. This molecule was tested in mice designed to be susceptible to colitis and diabetes mellitus.

Graphical summary of the principle of the study and its result. © D. VanDyke et al., 2022.

They found that the protein provided the animals with significant protection against the development of the respective autoimmune diseases. Specifically, F5111 IC promoted Treg activation and expansion.

The study’s lead author, Derek VanDyke, a PhD student in the Department of Chemical and Biomolecular Engineering, explains: In an autoimmune disease, your own immune system is basically attacking you, and these Tregs are used to suppress that attack. “.

The authors state that since autoimmune diseases are the result of the body’s defense system malfunctioning, suppressing this response could help prevent disease manifestations. They therefore plan to demonstrate the generality of F5111 IC by testing it in additional settings such as models of transplant rejection and an experimental model of autoimmune encephalomyelitis in multiple sclerosis.

Since early detection and prevention are not always possible, these results provide a blueprint for the design of Treg-biased immunotherapy that could be clinically translated into the treatment of autoimmune diseases.

source: Cell messages

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