"It's a system in perfect tension," said Regev. "It both suppresses and promotes Th17 cell creation, keeping the cells at equilibrium."
Through this analysis, one particular gene stood out to the researchers: SGK1. The gene plays an important role in the cells' development, and when turned off in mice, Th17 cells are not produced.
SGK1 had not been described in T cells before, but it has been found in cells in the gut and in kidneys, where it plays a role in absorbing salt.
Based on this, two teams of researchers set out to test the connection between salt and autoimmunity Kuchroo, Regev, and their colleagues working with mouse cells and mouse models, and Hafler's team working with human cells.
Through efforts led by co-first author and Brigham and Women's Hospital postdoc Chuan Wu, the team found that they could induce more severe forms of autoimmune diseases, and at higher rates, in mice fed a high-salt diet than in those that were fed a normal mouse diet. Kuchroo notes though that the high-salt diet alone did not cause autoimmune diseases the researchers had to induce disease, in this case by injecting a self-antigen to prompt the mouse immune system to respond.
"It's not just salt, of course," Kuchroo said. "We have this genetic architecture genes that have been linked to various forms of autoimmune diseases, and predispose a person to developing autoimmune diseases. But we also suspect that environmental factors infection, smoking, and lack of sunlight and Vitamin D may play a role. Salt could be one more thing on the list of predisposing environmental factors that may promote the development of autoimmunity."
"One important question is: how can one think of these results in the context of human health?"
|Contact: Haley Bridger|
Broad Institute of MIT and Harvard