Our eyes are considered ‘immune privileged’, which means that they are generally protected from our own immune system. The major mechanism for eye immune privilege comes from a tight physical barrier that separates our lymphocytes, such as T cells, from the actual eye. T cells do have the ability to cross this barrier, but they first must come in contact with, and be activated by eye antigens. These antigens are sequestered on the opposite side of the barrier, in the eye, so that they are not exposed to the T cells. There are diseases in which these retinal T cells do mysteriously become activated though, and they cause an inflammatory disease known as uveitis. Uveitis is responsible for causing blindness and other eye issues in many people, but again the cause for the T cell activation is largely unknown. Researchers at the NIH recently created a mouse model for uveitis, and were able to test a variety of factors that may be activating the T cells. To their surprise, the gut microbiota seemed to be activating the T cells. They published the results of their study last week in the journal Immunity.
The researchers first created a mouse model of uveitis where the retinal T cells spontaneously become activated. They then noticed that the highest concentration of these T cells were near the gut, suggesting the gut bacteria were playing a role. The scientists then treated the mice with antibiotics to decrease the gut bacterial concentration. Although the mice still developed some symptoms of uveitis, the disease was ameliorated greatly in these mice. As previously discussed, the normal T cell activator antigen is in the and physically separated. In order to ensure that this antigen wasn’t somehow leaking out of the eye to activate the T cells in their model they created mice that lacked these antigens in their eye. Still though, the mice presented symptoms of uveitis, meaning that the antigen that is activating the T cells is not from the eye, but rather is being produced somewhere else, such as the gut. In order to firmly prove the gut bacteria’s role, the scientists showed that T cells could be activated by specific proteins from gut bacteria. In fact, germ free mice, which otherwise would not have an ocular inflammatory response in their model, showed strong uveitis when they were given just the protein extract from other wild type mice.
This research is the first to connect the gut microbiome with ocular autoimmune inflammation. It presents many questions as to how to therapeutically combat this disease, perhaps through monitoring the gut microbiota for presentation of antigens that could activate these retinal T cells. It also begs to be connected with other sites immune privilege breakdown in the body. The fetus and placenta in pregnant women, for example, is an immune privileged space. Immune activation of this site can sometimes lead to miscarriage. Are gut or vaginal bacteria involved with this response, as we have discussed a few times in this blog? In time, scientists will know enough to accurately answer this question.