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Autoimmune disease triggered if T cells miss a single protein early on

ew study, the researchers carried out a detailed analysis of the autoimmune attack that is directed against the eye in Aire-deficient mice. What the team found was that the immune system was mainly targeting a single eye protein called IRBP despite the fact that several eye-specific proteins were missing in the thymus of Aire knockout mice. The team then went on to show that IRBP was expressed in the thymus under the control of Aire and that knockout mice lacking the IRBP protein were protected from the disease because they don't express the protein that the immune system is targeting.

In a key, final part of the new study, Anderson and his colleagues showed that if mice without a thymus gland ?so-called "nude" mice ?received a normal thymus lacking only IRBP, they developed the autoimmune eye disease. The autoimmune attack occurred even though the mice had normally functioning IRBP in their retinas. The final finding demonstrated that failure of T cells in the thymus to recognize IRBP as a self-protein was sufficient to cause the autoimmune disorder in the retina.

The scientists hope that better understanding of interactions in the thymus can lead to earlier, more effective treatment of autoimmune diseases.

"When we see autoimmune disease in the clinic, we are usually looking at it in a relatively late stage. Tissue is already damaged, antigen expression is ramped up and the immune response is spreading to other self-antigens," Anderson said. "If we can also train our focus on the thymus, where we know at least some of the autoimmune disease is triggered, we may be able to determine just what self-antigens are important and shut down the autoimmune process targeting those self -antigens."

The team is collaborating with Jeffrey Bluestone, PhD, director of the UCSF Diabetes Center, in preclinical studies to see if T cell autoimmune attacks on IRBP can be modulated to prevent the autoimmune eye disease.


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Source:University of California - San Francisco


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