Salt Consumption Allegedly Linked to Autoimmune Disorders
Two groups of researchers have allegedly provided evidence that sodium induces the differentiation of CD4 T cells responsible for immune responses, thereby raising concerns about the role of salt intake in autoimmune disorders. Both published in Nature, the two studies in question suggested that “a high-salt diet can enhance the differentiation of a class of immune cells called TH17 cells, and exacerbate disease in a mouse model of multiple sclerosis called experimental autoimmune encephalitis (EAE),” according to a concurrent news item. In addition, the authors apparently found that mice lacking serum glucocorticoid kinase 1 (SGK1), which plays a role in EAE, had reduced neuropathy and some protection from a high-salt diet.
In particular, the first study examined how increased sodium chloride concentrations in vivo “markedly boost the induction of murine and human TH17 cells,” purportedly showing that the TH17 cells generated under these conditions “display a highly pathogenic and stable phenotype characterized by upregulation of the pro-inflammatory cytokines GM-CSF, TNF-α and IL-2.” Markus Kleinewietfeld, et al., “Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells,” Nature, March 2013. Taken with the knowledge that “mice fed a high-salt diet develop a more severe form of EAE,” these results evidently persuaded the authors that “increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic TH17 cells.”
Meanwhile, the second study on the induction of pathogenic TH17 cells focused on SGK1’s role “in regulating IL-23R expression and stabilizing the TH17 cell phenotype by deactivation of mouse Foxol, a direct repressor of IL-23R expression.” Chuan Wu, et al., “Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1,” Nature, March 2013. Although “the precise molecular mechanism by which IL-23 sustains the TH17 response and induces pathogenic effector functions” remains unknown, the authors reported that “a modest increase in salt concentration induces SGK1 expression, promotes IL-23R expression and enhances TH17 cell differentiation in vitro and in vivo, accelerating the development of autoimmunity.”
Despite these initial findings, the Nature news item summarizing the two studies ultimately concluded that dietary salt is just one environmental factor associated with pathogenic TH17 cell development. “So, although these are exciting and provocative data, it is clearly premature—as also pointed out by both sets of authors—to state that dietary salt influences autoimmune disease in people, and that this is mediated by T-cell-induced production of IL-17,” write the article’s authors. “However, the work should spur investigation of tangible links between diet and autoimmune disease in people.”
