Researchers at Yale uncovered a way that high-salt diets may trigger inflammation and possibly contribute to the development of autoimmune diseases such as multiple sclerosis (MS).
Their study, “Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity,” was recently published in the journal Nature Immunology.
This link involves a specific type of immune cell called Tregs, or regulatory T-cells. There are several different types of T-cells that work together to maintain a functioning, but not hyperactive, immune system. Treg cells, as their name implies, regulate other T-cells, and suppress the immune response. In this way, Treg cells prevent aberrant autoimmunity.
In patients with MS or other autoimmune disorders, the number of Treg cells is often normal, suggesting that it is the activity of these cells that is altered in disease.
Treg activity can be measured by the production of specific circulating signaling molecules or cytokines. For instance, production of IFN-γ indicates dysfunctional Tregs, and it is seen in patients with autoimmunity disorders and in cancer. Tregs that produce the IL-10 cytokine are active and suppress the immune response. Therefore, the balance between IFN-γ and IL-10 production in Treg cells is central in maintaining a healthy immune system.
Autoimmune disorders such as MS result from a combination of genetic and environmental factors. Several environmental factors reported to be associated with an increased MS risk include vitamin D insufficiency, smoking, obesity, and a high-salt diet.
Mouse studies have shown that high-salt diets disrupt the workings (function) of Tregs by increasing IFN-γ expression.
In the current study, the link between a high-salt diet and autoimmunity is further explored, and a precise mechanism is defined. Researchers show that the balance between IFN-γ and IL-10 is skewed toward non-functioning Tregs and IFN-γ production in both samples from MS patients and mouse models on a high-salt diet.
To better understand why this balance is skewed, researchers screened a large number of genes and identified one protein, β-catenin, as a central player in regulating Treg function. β-catenin is part of a signaling pathway known to contribute to inflammation and cancer progression.
More in-depth analysis revealed that β-catenin works with another molecule called PTGER2 (prostaglandin E receptor 2), which is uniquely upregulated in response to high-salt conditions. These two molecules activate each other to maintain a pro-inflammatory environment by modulating Treg function.
“Our findings reveal a novel PTGER2–β-catenin loop in Treg cells linking environmental high-salt conditions to autoimmunity” including MS, the researchers concluded.