Increased dietary salt intake can induce a group of aggressive immune cells that are involved in triggering and sustaining autoimmune diseases. This is the result of a study conducted by an international group of scientists, including ones from Yale University, the Broad Institute, MIT, Harvard University, Vanderbilt University, the Max-Delbrück Center for Molecular Medicine in Berlin, and the University of Erlangen-Nuremberg, among others. The authors of the report, which was published online in Nature on March 6, 2013, included Dr. Markus Kleinewietfeld, Professor David Hafler, Dr. Ralf Linker, Professor Jens Titze, and Professor Dominik N. Müller. A second study, published on the same day in Nature, describes how a salt-sensing enzyme might be involved in the induction of autoimmune disease. A third study, also published on the same day in Nature, describes the molecular pathways involving T helper cells that can lead to autoimmune disease. Together, this suite of three Nature articles may significantly advance our understanding of the origins of autoimmune disease. The focus here is on the first article on the effects of excess dietary salt. In recent decades, scientists have observed a steady rise in the incidence of autoimmune diseases in the Western world. Because this increase cannot be explained solely by genetic factors, researchers hypothesize that the sharp increase in these diseases is linked to environmental factors. Among the suspected culprits are changes in lifestyle and dietary habits in developed countries, where highly processed food and fast food are often on the daily menu. These foods tend to have substantially higher salt content than home-cooked meals.
Increased dietary salt intake can induce a group of aggressive immune cells that are involved in triggering and sustaining autoimmune diseases. This is the result of a study conducted by an international group of scientists, including ones from Yale University, the Broad Institute, MIT, Harvard University, Vanderbilt University, the Max-Delbrück Center for Molecular Medicine in Berlin, and the University of Erlangen-Nuremberg, among others. The authors of the report, which was published online in Nature on March 6, 2013, included Dr. Markus Kleinewietfeld, Professor David Hafler, Dr. Ralf Linker, Professor Jens Titze, and Professor Dominik N. Müller. A second study, published on the same day in Nature, describes how a salt-sensing enzyme might be involved in the induction of autoimmune disease. A third study, also published on the same day in Nature, describes the molecular pathways involving T helper cells that can lead to autoimmune disease. Together, this suite of three Nature articles may significantly advance our understanding of the origins of autoimmune disease. The focus here is on the first article on the effects of excess dietary salt. In recent decades, scientists have observed a steady rise in the incidence of autoimmune diseases in the Western world. Because this increase cannot be explained solely by genetic factors, researchers hypothesize that the sharp increase in these diseases is linked to environmental factors. Among the suspected culprits are changes in lifestyle and dietary habits in developed countries, where highly processed food and fast food are often on the daily menu. These foods tend to have substantially higher salt content than home-cooked meals. This particular study is the first to indicate that excess salt intake may be one of the environmental factors driving the increased incidence of autoimmune diseases. A few years ago, Professor Titze showed that excess dietary salt (sodium chloride) accumulates in tissue and can affect macrophages (a type of scavenger cell) of the immune system. Independent of this study, Dr. Kleinewietfeld and Dr. Hafler observed changes in CD4-positive T helper cells (Th) in humans, which were associated with specific dietary habits. The question arose whether salt might drive these changes and thus can also have an impact on other immune cells. Helper T cells are alerted of imminent danger by the cytokines of other cells of the immune system. They activate and “help” other effector cells to fight dangerous pathogens and to clear infections. A specific subset of T helper cells produces the cytokine interleukin-17 and is therefore called Th17 for short. Evidence is mounting that Th17 cells, apart from fighting infections, play a pivotal role in the pathogenesis of autoimmune diseases. In cell culture experiments the researchers showed that increased sodium chloride can lead to a dramatic induction of Th17 cells in a specific cytokine milieu. “In the presence of elevated salt concentrations, this increase can be ten times higher than under usual conditions,” Dr. Kleinewietfeld and Professor Müller explained. Under the new high salt conditions, the cells undergo further changes in their cytokine profile, resulting in particularly aggressive Th17 cells. In mice, increased dietary salt intake resulted in a more severe form of experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Multiple sclerosis is an autoimmune disease of the central nervous system in which the body’s own immune system destroys the insulating myelin sheath around the axons of neurons and thus prevents the transduction of signals, which can lead to a variety of neurological deficits and permanent disability. Recently, researchers have postulated that autoreactive Th17 cells play a pivotal role in the pathogenesis of multiple sclerosis. Interestingly, according to the researchers involved in the current study, the number of pro-inflammatory Th17 cells in the nervous system of the mice increased dramatically under a high-salt diet. The researchers showed that the high-salt diet accelerated the development of helper T cells into pathogenic Th17 cells. The researchers also conducted a closer examination of these effects in cell culture experiments and showed that the increased induction of aggressive Th17 cells is regulated by salt on the molecular level. “These findings are an important contribution to the understanding of multiple sclerosis and may offer new targets for a better treatment of the disease, for which at present there is no known cure,” said Dr. Linker, who as head of the Neuroimmunology Section and Attending Physician at the Department of Neurology, University Hospital Erlangen, seeks to utilize new laboratory findings for the benefit of patients. Besides multiple sclerosis, Professor Müller and his colleagues want to study psoriasis, another autoimmune disease with strong Th17 components. The skin, as Professor Titze recently discovered, also plays a key role in salt storage and affects the immune system. “It would be interesting to find out if patients with psoriasis can alleviate their symptoms by reducing their salt intake,” the researchers said. “However, the development of autoimmune diseases is a very complex process which depends on many genetic and environmental factors,” the immunologist Dr. Markus Kleinewietfeld said. “Therefore, only further studies under less extreme conditions can show the extent to which increased salt intake actually contributes to the development of autoimmune diseases.” [Press release] [Nature abstract 1] [Nature abstract 2] [Nature abstract 3] [Nature News] [Nature News & Views]
