New Studies on the Role of Salt in Autoimmunity
March 13, 2013
Background: The Role of Dietary Salt in Autoimmune Diseases
Autoimmune diseases like MS are defined as inappropriate immune responses to cells and tissues in the body. Much work has been done to identify the types of cells involved in these responses, as well as genetic abnormalities that alter cell behavior. New studies are now looking at the role of environmental and lifestyle factors in driving autoimmune diseases, especially in light of the notable increase in these diseases over the last few decades.
Three studies were published in the prestigious scientific journal Nature examining the effects of salt (NaCl2) on immune activity. Overall the results of their experiments show that increased concentrations of salt lead to the production of a specific type of T cell involved in autoimmunity. This group of T cells, known as Th17 cells, has also been implicated in the development of EAE which is an animal model that mimics MS disease.
Dr. David Hafler, Dr. Markus Kleinewietfeld (Yale University and Broad Institute of MIT and Harvard), Dr. Vijay Kuchroo, Dr. Aviv Regev, Dr. Chuan Wu (Harvard Medical School and Broad Institute of MIT and Harvard), Dr. Regev, Kuchroo and Dr. Nir Yosef (Broad Institute of MIT and Harvard) report on the effects of salt on Th17 cells using a variety of advanced techniques both in cell culture and in animal models.
Dr. Hafler’s team exposed naïve T cells (immune cells which have not yet developed into specific subtypes) to increased salt concentrations. They noticed that this stimulated the naïve cells to become the Th17 cells, which play a major role in autoimmunity. The results demonstrated that the presence of salt led to the expression of molecules that promote inflammation, which is what causes damage in autoimmune diseases like MS. For example, levels of the molecule CCR6 were elevated after the administration of salt; CCR6 is required for Th17 cells to function. The researchers also explored the effects of a high-salt diet in mice which develop MS-like disease. The results showed that a modest increase in salt levels sped up the onset of EAE and increased disease severity.
Dr. Kuchroo’s team observed the effects of salt on a protein called “serum glucocorticoid kinase-1” (SGK1), which a molecule that drives the harmful effects of Th17 cells. The study reports that an increase in salt concentrations led to greater levels of the SGK1 protein, which resulted in an increased expression of molecules that promote the development of Th17 cells. In a follow-up experiment, normal mice as well as mice lacking the SGK1 protein were fed a high salt-diet. After 3 weeks, researchers noticed that mice that did not have SGK1 exhibited lower levels of Th17 cells as well as a reduction in EAE severity.
The final study conducted by Dr. Regev’s team provides evidence on the highly intricate network of signaling molecules that govern the response of the Th17 cells. A key player in this network is IL-17, which has shown to play an important role in high-salt induced autoimmunity as described in the paper from Dr. Kuchroo’s group.
This research collectively illustrates the important role of Th17 cells in autoimmunity. The activity of these cells depends on mechanisms that are governed by a number of signals. Understanding this pathway is key in developing new therapies for autoimmune diseases like MS. The link between Th17 cell activity and salt is a new line of evidence that probes the relationship between autoimmune diseases and environmental factors such as diet. It is important to bear in mind that the clinical and regulatory significance of this work is yet to be determined as these experiments are still being done in a laboratory setting. Further research is required to determine if dietary salt does in fact have an effect on MS disease activity.
Kleinewietfeld M et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature, 2013 Mar 6 [Epub ahead of print]
Wu C et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature, 2013 Mar 6 [Epub ahead of print]
Yosef N et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature, 2013 Mar 6 [Epub ahead of print]
National Research and Programs
Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis
March 4, 2013
Background: Vitamin D and MS
Recent studies have illustrated a relationship between levels of vitamin D and multiple sclerosis disease activity as seen through clinical and MRI measures. Aside from its role in promoting calcium absorption and overall good bone health, vitamin D has also been shown to have a direct effect on the immune system. The immunoregulatory function of vitamin D, including its ability to inhibit T and B cell activity, has prompted ongoing research into its impact on disease course and treatment of autoimmune diseases like MS.
The human body is able to produce vitamin D with the help of sufficient exposure to UVB-radiation. Natural human levels of vitamin D are therefore dependent on factors such as: amount of sun exposure, use of sun protection, geographical location, skin colour, age, sex, and genetic factors. A person’s level of vitamin D can also be increased through intake of vitamin D-enriched foods and supplements.
Several lines of evidence have reported associations between vitamin D with relapse rates, changes in disability, and risk of MS. The goal of this study was to assess the relative contribution of environmental factors such as sun exposure and vitamin D supplementation to vitamin D levels in people with MS. The study also aims to ascertain the relationship between sun exposure and MRI measures of neurodegeneration.
The study, led by a team of scientists from the Department of Neurology at the State University of New York in Buffalo, included 264 people with MS and 69 healthy controls. Subjects underwent neurological and MRI examinations and provided blood samples. Information on race, skin and eye colour, supplement use, body mass index (BMI) and sun exposure history was obtained through a questionnaire. Levels of vitamin D were measured using mass spectrometry.
What they found:
Results of the study revealed that vitamin supplementation, sun exposure, eye colour and BMI were associated with changes in vitamin D levels in people with MS. The study also showed that longer sun exposure was associated with a significant increase in brain volume in people with MS compared to healthy controls. The researchers speculate that changes in the immune system resulting from exposure to the sun may lead to changes in brain volume and other MRI measures of MS. The main limitation of their research was that it was a cross-sectional study, meaning that the investigators are collecting information from the subjects at a specific point in time. This may lead to past lifestyle changes having an effect on the results observed.
This study adds to the growing body of research that highlights the relationship between vitamin D and MS. Although research on vitamin D has shown that its effect on the immune system bears implications in reducing disease severity, it is important to keep in mind that the results are not conclusive. Thus, further research in this area as well as on the therapeutic benefit of vitamin D is required.
Source: Zivadinov R et al. Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry, 2013 Feb 5 [Epub ahead of print]