doi:10.1038/nindia.2016.40 Published online 22 March 2016
Limiting nutrients to the body could boost vaccine-induced immunity and control intestinal inflammation, according to new study by Indian and US researchers1. The results may be promising for treatment of inflammatory bowel diseases, and autoimmune diseases such as rheumatoid arthritis and psoriasis.
The researchers were trying to figure out how the body adapts to nutrient scarcity. The enzyme general control nonderepressible 2 (GCN2) is known to play a critical role in sensing changing nutrient levels in the gut and helping maintain the immunological balance. They discovered that mice lacking GCN2 are more sensitive to the chemical irritant DSS (dextran sodium sulfate), often used to model colitis in animals. In the absence of irritants, the intestines in mice lacking GCN2 looked normal.
Mice when fed a low protein diet or a diet lacking only the amino acid leucine were protected from signs of colitis, such as weight loss and bloody diarrhoea. Mice lacking GCN2 were not protected from colitis when fed a low protein diet. This, the researchers say, demonstrates that GCN2 is necessary for the protective effect.
The researchers have shown that responses of TH17 immune cells, important in several autoimmune diseases, are controlled by GCN2. They say targeting the GCN2 pathway may provide new strategies of treating inflammatory bowel disease and other inflammatory disorders.
1. Ravindran, R. et al. The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation. Nature (2016) doi: 10.1038/nature17186