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USC CiMUS research describes a new mechanism essential in the onset of type 1 diabetes

  • This finding, published in the international journal Nature Communications, suggests the need to study autoreactivity in healthy people in order to identify which signal initiates the disease.


Understanding the origin of type 1 diabetes in order to advance the development of therapies that open the way to new, more effective drugs that contribute to delaying the onset of this disease is a recurring line of research, since insulin is, to date, the only treatment for this autoimmune disease. Now, the Immunity and Small Molecules group at CiMUS at USC, in collaboration with King's College London (United Kingdom) and Technische Universitat Dresden (Germany), has succeeded in opening a new line of study focused on understanding the characteristics of TCR proteins that cause incorrect recognition of autoantigens, leading to the destruction of pancreatic cells that produce insulin. The work has just been published in the prestigious international journal Nature Communications.

“This process of mistaken destruction begins when a type of immune cell, T lymphocytes, recognises self-antigens (“autoantigens”) as if they belonged to foreign agents such as viruses or bacteria. This recognition is carried out through proteins called TCRs (“T cell receptors”) that bind to antigens like a key to a lock, so that, if they locate the antigen for which they are specific, they are activated and the destructive process begins. Therefore, the key to understanding the cause of autoimmune diseases, and thus being able to develop better therapies, is to understand what characteristics these TCRs have in patients and what causes this mistaken recognition of autoantigens,” explains CiMUS researcher Iria Gómez Touriño.

 

Physiological vs. pathogenic autoimmunity

Autoimmune diseases are those in which the immune system mistakenly destroys its own cells. There are more than 100 autoimmune diseases described and their incidence is increasing at an ever-increasing rate. These diseases include, among others, rheumatoid arthritis, Crohn's disease and type 1 diabetes.

The research team was able to verify in this study that these autoreactive cells are present in healthy people, that they are very frequent and that they are activated because they have recognized a pancreatic antigen. “This discovery was completely unexpected, since the dogma in the field of autoimmunity is that people without autoimmune diseases should not have these autoreactive cells,” says Gómez Touriño.

In a more detailed analysis, using cutting-edge sequencing techniques, they observed that these TCRs are different between patients and healthy donors. Specifically, a set of TCRs that do appear in healthy people are not present in patients, and the patients' cells have different characteristics, expressing more or less some specific genes, suggesting that there is a physiological and a pathogenic autoimmunity.

All of this led the team to formulate a new model of autoreactivity in type 1 diabetes according to which the death of pancreatic cells during the period immediately after birth is necessary for the correct formation of the newborn's pancreas.

"Thus, our defenses develop an immunological memory against these cells, a memory that, in healthy donors, remains under control for the rest of life. However, in people who later develop type 1 diabetes, this memory that is generated is imperfect and too prone to reactivation and, in addition, is not controlled correctly, leading to the massive destruction of pancreatic cells," explains the researcher.

This study therefore sheds light on the initial mechanisms that lead to the appearance of type 1 diabetes and highlights the importance of studying autoreactivity in people without autoimmune diseases in order to differentiate physiological and pathological autoreactivity.

Diabetes in children

CiMUS researcher Iria Gómez Touriño focuses her research on childhood and juvenile diabetes. “It is a disease that has nothing to do with children and young adults eating poorly, that is type II diabetes. Diabetes in children is conditioned by the fact that their immune system becomes confused and kills the pancreas. By doing so and killing the cells of the pancreas, it cannot produce insulin,” she points out.

The Immunity and Small Molecules group at CiMUS at USC seeks to advance knowledge of the mechanisms that cause this disease, using novel molecular and sequencing techniques, proposing an alternative explanation for the causes underlying the autoimmune process that characterises this pathology.

About CiMUS

The Unique Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) at the University of Santiago de Compostela is part of the network of research centres with a new organisation and operation model, which constitutes the fundamental element of the R&D strategy of the CAMPUS VIDA project (Campus of International Excellence, MEC-MICINN, 2009). The mission of CiMUS is to carry out basic research of proven quality, with the aim of achieving advances in the prevention, understanding and treatment of chronic disease. The centre has CIGUS recognition from the Xunta de Galicia, which accredits the quality and impact of its research. More information on the website https://cimus.usc.gal/ or follow us on social media @cimususc (Twitter, Instagram and LinkedIn).