Negative effect: A diet that is too high in salt can weaken the energy supply of important control cells in our immune system – and thereby promote autoimmune reactions and inflammation, as a study shows. So excess salt impairs the regulatory T cells that normally keep our immune responses in check. However, the salt disrupts their mitochondrial function and gene activity. As a result, these cells are no longer able to fight excessive immune reactions as well.
Too much salt is unhealthy – this is not new. Excessive salt intake can increase blood pressure and damage the cardiovascular system. Cerebral blood flow and mental performance could also suffer from long-term excess salt, as studies with mice suggest. In 2021, scientists also discovered that too much salt can also damage the immune system: because salt disrupts the function of the mitochondria, the scavenger cells required to defend against pathogens no longer function properly.
Regulatory T cells at a glance
It has now been shown that the immune system’s control of excessive, pathological reactions is also disrupted by an excess of salt. “The starting point were observations in autoimmune patients and our results, according to which salt restricts the function of the mitochondria in monocytes and macrophages,” explains co-author Dominik Müller from the Max Delbrück Center in Berlin. “We asked ourselves whether similar problems can occur in the regulatory T cells of healthy people.”
Regulatory T cells, or Tregs for short, are an important control factor in our adaptive immune system. They inhibit aggressive immune cells that turn against their own body and thus ensure that immune reactions do not get out of control. In some autoimmune diseases, such as multiple sclerosis, the Tregs work only to a limited extent, which can lead to immune-related inflammation and damage to the body’s own tissues.
For their study, Müller, first author Beatriz Côrte-Real from the University of Hasselt in Belgium, and their team investigated whether excess salt can also affect the regulatory T cells. To do this, they analyzed how the function of the mitochondria and gene activity in cultures of human Tregs changed when the salt content of the nutrient medium increased.
Energy metabolism and function deteriorated
And indeed: If the regulatory T cells are exposed to a higher salt content, their energy metabolism deteriorates measurably, as the researchers found. The mitochondria of the affected Tregs produced less chemical energy, resulting in a shift in cell metabolism and impaired immune cell function. The “oversalted” regulatory T cells thus resembled those known from patients with autoimmune diseases.
The team was also able to find out how the salt inhibits the function of the mitochondria: “The high extracellular salt content increases the concentration of sodium ions in the cell,” Côrte-Real and her team explain. “This inhibits the respiration of the mitochondria because it disrupts their electron transport chain.” In the further course, this leads to a lack of energy in the Tregs and changes in their gene expression. In the study, even a brief disruption in mitochondrial function had long-lasting consequences for the immune-regulating capacity of the Tregs.
Possible risk factor for autoimmune diseases
According to the researchers, this indicates that a diet that is too high in salt affects not only the scavenger cells of the immune system but also the regulatory T cells and may contribute to Treg malfunctions in various diseases. “To better understand the factors and molecular mechanisms that contribute to Treg dysfunction in autoimmunity is a key question in this field,” says co-author Markus Kleinewietfeld from the University of Hasselt.
Since regulatory T cells also play a role in diseases such as cancer or cardiovascular diseases, the elucidation of such salt-triggered effects could open up novel approaches to alter Treg function in various diseases, the researcher continues. “However, further studies are needed to better understand the molecular mechanisms and their potential association with disease.” (Cell Metabolism, 2023; doi: 10.1016/j.cmet.2023.01.009)
Source: Max Delbrück Center for Molecular Medicine in the Helmholtz Association