Gut bacteria may provide the trigger for autoimmune uveitis, a destructive inflammation of the eye, researchers at the US National Eye Institute (NEI) reported in a study published today (August 18) in Immunity. Autoimmune uveitis is a painful condition that can lead to debilitating blindness. It often hits adults 20 to 60 years old, and is responsible for up to 15 percent of all blindness and severe visual impairment in developed countries.
The team also found that the model mouse intestines showed high levels of interleukin-17A, a proinflammatory cytokine produced by T cells. In another experiment, the researchers administered a wide-spectrum antibiotic cocktail to the mice in an effort to reduce the gut microbiome. The antibiotics appeared to slow the development of uveitis in the mice and reduce the number of activated T cells. The researchers also found that microbe-rich extracts from model mouse intestines activated retina-specific T cells.
“It’s been known for other autoimmune diseases that gut bacteria can provide a necessary component, but the mechanism wasn’t known,” Caspi told The Scientist. “What appears to be happening is that they make some substance that, to the T-cells, looks like a protein from the retina.”
The researchers were unable, however, to identify the specific proteins or the bacteria that might produce this substance, which Caspi noted was a limitation of the study. It may be that a combination of bacteria work together to trigger the retina-specific T-cells, making the task of identifying the responsible proteins and bacteria even more challenging, she added.
The team was also unable to directly demonstrate that the retina-specific T helper cells in the gut are the same cells circulating to the eye—breaching the immune-privileged barrier to cause inflammation and disease, noted Veena Taneja, an immunologist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study. “They have not shown that these cells are the cells that cause disease,” she said. “And they have not shown that these cells are actually being activated in gut.”
Caspi said the team plans to continue to isolate the specific bacteria and/or proteins involved in activating the retina-specific T cells. “We don’t know what that actual protein is and I don’t know how long it will take to find it,” she said. “It may that we have to search far and wide for this mimic.”
R. Horai et al., “Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site,” Immunity,doi:10.1016/j.immuni.2015.07.014, 2015.