Some microbes that naturally live in our intestines could be bad for us, triggering autoimmune uveitis, one of leading causes of blindness. A new study suggests that some residents of the intestine produce proteins that enable destructive immune cells to enter the eyes.
The idea that gut microbes can promote autoimmune uveitis "was there in the back of our minds," says immunologist Andrew Taylor Eye of Medicine Boston University School who was not connected to the research. "This is the first time it has been shown that the intestinal flora seems to be part of the process."
as many as 400 000 people in the US have an autoimmune uveitis, wherein the T cells of the immune commanders-invade the eye system and damage the interlayer. All of the T cells are triggered by specific molecules called antigens and T cells which cause 'autoimmune uveitis, ocular certain proteins are the antigens. Even healthy people carry these T cells, but they generally do not swarm the eyes and cause disease. This is because they must first be triggered with their corresponding antigen. However, these proteins are not normally leave the eye. So that could stimulate T cells? One possible explanation is microbes in the gut.
mouse In the new study, immunologist Rachel Caspi of the National Eye Institute in Bethesda, Maryland, and colleagues genetically engineered so that their T cells recognized the one of the same target protein in ocular autoimmune uveitis. The rodents have developed the disease in the time they were weaned. But dosing animals with four antibiotics that killed most of their gut microbes delayed the onset and reduced severity disease. The researchers found the same effects in so-called germ-free mice, which lack the intestinal bacteria.
To test whether gut microbes have been stimulating these T cells, Caspi and colleagues added the intestinal contents of sick mice with T cell cultures This intestinal viscous substance under voltage of the cells, priming for infiltration of the eye. The team wonders if a protein released by the intestinal microbes triggered T cells, so they then added a protein-destroying enzyme in the intestine mixture. The T cell response was lower, suggesting they were responding to a protein. In another experiment, the researchers injected T cells from genetically modified mice in control mice not prone to autoimmune uveitis. If these T cells was not exposed to intestinal material, they do not cause uveitis. But 86% of the animals developed an autoimmune uveitis if they received a high dose of T cells that had been exposed to the intestinal contents of the diseased mice, the researchers report online today in Immunity .
The results suggest that some bacteria in the intestines produce proteins that closely resemble those of the eye and can switch on T cells in the intestine. "We can prove that the activation occurs in the intestine," says Caspi. The activated cells then probably go in the eyes, they come and begin to destroy.
"It is a very rigorous, and it really adds to our knowledge" about the origins of autoimmune uveitis, ocular immunologist said Russell Read of the University of Alabama, Birmingham, who n has not participated in the study. One issue researchers must answer now is why we do not have all these autoimmune reactions in our retinas, says ocular immunologist James Rosenbaum of the Health & Science University in Portland Oregon. It is possible, he says, that only certain people have bacteria that stimulate T cells or genes that could leave some people vulnerable to the disease.
Caspi and his colleagues are still trying to find out which proteins the gut T cells recognize and bacteria produce them. "I am not suggesting that popping an antibiotic pill or take a probiotic will be a solution to the disease," she said. But identification of these molecular mimetics eye protein and bacteria that they were born, could help researchers develop new ways to treat or prevent autoimmune uveitis.
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