Is excess salt a risk factor for developing autoimmune diseases?

The results of the study of the role of T helper 17 immune cells in the development of immune reactions, conducted by an international group of researchers, demonstrated the existence of an unexpected relationship between the development of autoimmune diseases and salt intake.

The immune system must constantly be in a state of equilibrium, since too low its activity makes a person susceptible to infectious agents, and too high can cause allergic and autoimmune diseases. Violations of this delicate balance can lead to the development of autoimmune diseases.

The authors of the study wanted to understand how the body manages to maintain this balance, namely, to provide the strictly necessary number of certain types of immune cells that exhibit a certain level of activity. As an object of research, they chose T-helper-17 – immune cells discovered in 2005 and named for their ability to produce cytokine interleukin-17. These cells are involved in the development of inflammatory reactions that play an important role in protecting the body from various pathogens, but they are also known for their participation in the pathogenesis of allergic and autoimmune diseases, such as multiple sclerosis, psoriasis, rheumatoid arthritis and ankylosing spondylitis.

Previously, experts had already identified several genes involved in the maturation of T-helper-17, but the authors wanted to study this process in as much detail as possible. To do this, they analyzed the expression and activity of the genes of maturing T-helper-17 18 times within 3 days. Based on the data obtained, computational algorithms were developed that made it possible to integrate the ongoing molecular changes into the overall picture.

After that, the scientists systematically tested their model by alternating silencing (suppression of expression) of genes, which allowed them to identify the most important stages of the process and decipher their biological significance.

The RNA interference technology traditionally used to suppress gene expression using viral vectors was inapplicable in this case, as it led to irreversible changes in T cells or even their death. As an alternative, the method developed by the co-authors of the study was chosen, which consists in introducing the thinnest nanowires into the cells (in the figure), providing targeted delivery of the necessary molecules and practically having no effect on the state of the cell.

As a result, it was found that the maturation of T-helper-17 occurs under the influence of two signaling systems, the joint action of which is based on the equilibrium principle characteristic of the functioning of the immune system. One of these systems stimulates an increase in the number of these cells, suppressing the development of other types of immune cells, while the other has the opposite effect.

During the analysis, it was also found that the SGK1 gene plays a special role in the development of T-helper-17, the suppression of the expression of which completely blocked the production of these cells.

Previously, this gene was not seen to be involved in the functioning of T-lymphocytes, but it is known that it is expressed by intestinal and kidney cells, and its protein product is involved in the process of salt absorption.

Having found out this fact, the scientists decided to check whether there is a relationship between salt intake and autoimmunity. Experiments on mice have shown that by itself the use of excessive amounts of salt does not lead to the development of autoimmune diseases. However, when inducing such diseases by introducing an autoantigen that causes an inadequate response of the immune system, a diet with a high salt content increased the likelihood of developing the disease and aggravated its severity compared to that observed in the control group.

The authors note that many factors are involved in the development of autoimmune diseases, including numerous genes that provide a predisposition to various forms of autoimmune reactions. Environmental factors potentially contributing to the development of autoimmunity include infectious agents, smoking, as well as a lack of sunlight and vitamin D. Apparently, excessive salt intake is only one of such factors. To date, it is still too early to say: limit the use of salt, because it can lead to the development of autoimmune diseases. This hypothesis has yet to be confirmed through carefully planned epidemiological studies.

Currently, scientists are planning a new study, the purpose of which will be to identify potential therapeutic targets using the data obtained and to study the possibility of their use for the treatment of autoimmune diseases.

Articles by Yosef et al. Reconstruction of the dynamic regulatory network that controls Th17 cell differentiation by systematic perturbation in primary cells, Wu et al. Induction of pathogenic Th17 cells by inducible salt sensing kinase SGK1 and Kleinewietfeld M. et al. Sodium chloride drives autoimmune disease by the induction of pathogenic Th17 cells published in the journal Nature.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Broad Institute of MIT and Harvard:
Circuitry of cells involved in immunity, autoimmune diseases exposed. 

11.03.2013