Salt can impair the energy supply of immune regulators

A high-salt diet, as is common in many Western societies, not only affects blood pressure and the cardiovascular system. It can also have negative effects on the regulation of the immune system. This is because salt slows down regulatory T cells by impairing their energy metabolism. This is reported by an international research team in the scientific journal „Cell Metabolism“. The research project was coordinated by scientists from the VIB Centre for Inflammation Research, the University of Hasselt in Belgium and the Max Delbrück Centre in Berlin. The results could advance research into autoimmune and cardiovascular diseases.

A few years ago, the Belgian-German team showed that too much salt in our diet can have a negative impact on the metabolism and energy balance of certain cells of the innate immune system. Monocytes or macrophages then no longer function properly because salt weakens the mitochondria. Professor Dominik Müller from the Max Delbrück Center and Experimental and Clinical Research Center, a joint institution of Charité – Universitätsmedizin Berlin and the Max Delbrück Center, and Professor Markus Kleinewietfeld from the VIB Centre for Inflammation Research and the University of Hasselt in Belgium and their colleagues were involved in the studies. The research groups now wondered whether excessive salt consumption could trigger a similar problem in cells of the adaptive immune system such as regulatory T cells.

Important immune regulators
Regulatory T cells, or Tregs for short, are an essential component of the adaptive immune system. They maintain the balance between normal function and excessive inflammation. They are sometimes described as the 'immune police' because they keep 'belt' organisms, such as aggressive immune cells that target the body, in check. They ensure that immune reactions take place in a controlled manner - without damaging the organism.

A malfunction of the Tregs could lead to the development of autoimmune diseases such as multiple sclerosis. Researchers have recently shown that the mitochondria of the Tregs work less well in affected patients. However, the causes remained unclear.

„The observations in autoimmune patients and our findings that salt restricts the function of mitochondria in monocytes and macrophages were our starting point. We wondered whether similar problems could occur in the Tregs of healthy subjects," says Müller, head of the Hypertension-Mediated End Organ Damage research group at the Max Delbrück Centre and the ECRC.

Previous research has also shown that too much salt could impair Treg function by inducing an autoimmune-like response. In other words, too much salt makes Treg cells look more like those involved in autoimmune diseases. However, exactly how salt affects Treg functions was not yet known.

Salt disrupts the cellular power plants of the Tregs
The current international study led by Kleinewietfeld and Müller with first author Dr. Beatriz Côrte-Real and first author Dr Ibrahim Hamad – both working at the VIB Centre for Inflammation Research and at the University of Hasselt in Belgium – has now proven that salt is the main cause of inflammation: Salt disrupts Treg function by inhibiting energy production in mitochondria and altering cellular metabolism. The problem of „cellular power plants“ is apparently the first step in how salt disrupts Treg function and leads to changes in gene expression – äsimilar to dysfunctional Tregs in autoimmune diseases.

Even when mitochondrial function was only briefly disrupted, this had long-lasting consequences for the performance and immunoregulatory capacity of Tregs in various experimental models. The new findings suggest that salt may contribute to Treg dysfunction in various diseases. However, this needs to be confirmed in further studies.

„Understanding the factors and molecular mechanisms that contribute to Treg dysfunction in autoimmunity is a key question in this field. Since Tregs also play a role in diseases such as cancer or cardiovascular diseases, the elucidation of such salt-induced effects could open up novel approaches to alter Treg function in various diseases," says Kleinewietfeld, who heads the VIB Translational Immunomodulation Laboratory. „However, further studies are needed to understand the molecular mechanisms in more detail and to determine their potential links to disease.“

Original publication:
Beatriz Côrte-Real, Ibrahim Hamad et al. (2023): „Sodium perturbs mitochondrial respiration and induces dysfunctional Tregs“. Cell Metabolism, DOI: 10.1016/j.cmet.2023.01.009

Notification from "LABO" dated 13 February 2023