Excess salt cuts energy supply of immune regulators
Too much salt can disrupt the energy metabolism in regulatory immune cells
February 7, 2023
Eating too much salt is not only bad for our blood pressure and cardiovascular system. It could also impact the immune system. An international research team, coordinated by scientists at VIB and Hasselt University (Belgium), as well as the Max Delbrück Center in Berlin (Germany), now reports in Cell Metabolism that salt can disturb important immune regulators called regulatory T cells by upsetting their energy metabolism. The findings may provide new avenues to explore the development of autoimmune and cardiovascular diseases.
A few years ago, research by the teams of Prof. Dominik Mueller at the Max Delbrück Center for Molecular Medicine and the Experimental and Clinical Research Center, a joint institution of Charité – Universitätsmedizin Berlin in Germany, and Prof. Markus Kleinewietfeld of the VIB Center for Inflammation Research & Hasselt University, Belgium, and colleagues revealed that too much salt in our diet, common in many Western societies, can disrupt the metabolism and energy balance in innate immune cells, called monocytes/macrophages, which stops them from working properly. They showed that salt induces malfunctions in the mitochondria, the power plants in our cells. Inspired by these findings, the research groups wondered whether excessive salt also creates a similar problem in adaptive immune cells, like regulatory T cells.
Important immune regulators
Regulatory T cells, also known as Tregs, are an essential part of the adaptive immune system and they are responsible for maintaining the balance between normal function and unwanted, overreaching inflammation. They are sometimes referred to as the 'immune police' that keep the bad guys (autoreactive immune cells) at bay and ensure that immune responses happen in a controlled way without harming the host organism.
The deregulation of Tregs is believed to be linked to the development of autoimmune diseases, like multiple sclerosis. Interestingly, recent research observed problems in mitochondrial function of Tregs from patients with autoimmunity but contributing factors remained elusive.
Prof. Dominik Mueller (Max Delbrück Center and the Experimental and Clinical Research Center in Berlin, Germany) explains: "Considering our previous findings of salt affecting the mitochondrial function of monocytes/macrophages and the new observations on mitochondria in autoimmune Tregs, we were wondering if sodium may elicit similar issues in Tregs."
Salt interferes with mitochondrial function of Tregs
Previous research has already shown that excess salt could impact Treg function by inducing an autoimmune-like phenotype. In other words, too much salt makes the Treg cells look like those involved in autoimmune conditions. However, the exact way sodium impairs Treg function has not been uncovered.
The new international study led by Prof. Kleinewietfeld and Prof. Mueller and first authored by Drs. Beatriz Côrte-Real and Ibrahim Hamad (VIB Center for Inflammation Research & Hasselt University, Belgium), now discovered that sodium disrupts Treg function by altering cellular metabolism through interference with mitochondrial energy generation. This mitochondrial problem seemed to be the initial step in how salt alters Treg function, leading to changes in gene expression that showed similarities to those of dysfunctional Tregs in autoimmune conditions.
Even a short-term disruption of mitochondrial function showed long-lasting consequences for the fitness and immune-regulating capacity of Tregs in experimental models. The new findings suggest that sodium may be a factor that could contribute to Treg dysfunction, potentially playing a role in different diseases, although this needs to be confirmed in further studies.
Prof. Markus Kleinewietfeld (VIB Center for Inflammation Research & Hasselt University, Belgium): “The better understanding of factors and underlying molecular mechanisms contributing to Treg dysfunction in autoimmunity is an important question in the field. Since Tregs also play a role for example in cancer or cardiovascular diseases, the further exploration of those sodium-elicited effects may offer novel strategies to alter Treg function in different types of diseases. However, future studies are needed to understand the molecular mechanisms in more detail and to clarify their potential relation to disease.”
Publication
Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs. Côrte-Real, Hamad, et al. Cell Metabolism, 2023. doi: 10.1016/j.cmet.2023.01.009
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