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

isease," he added.

A similar mechanism may be at play involving other autoimmune diseases such as type 1 diabetes, Anderson said. Immunologists have demonstrated that insulin is expressed in the thymus ?not just in the pancreas. Studies have shown that people who are protected from diabetes express high levels of insulin in the thymus, while those who are predisposed express lower levels of insulin in this organ.

"What we think is that 'more is better' in the thymus," Anderson says. "If you have more insulin in the thymus, then there is a better chance that potentially destructive insulin-specific T cells will encounter insulin as self and be filtered out."

In the thymus, immature T cells display on their surface many thousands of unique receptors, generated by random gene rearrangements. This strategy allows the receptors to recognize the tremendous diversity of invading pathogens. In the process, however, they also develop receptors that bind to the body's own proteins. These T cells are normally eliminated, avoiding the plague of autoimmunity.

A clue to how the elimination process is controlled came from previous work involving a protein in the cell nucleus called Aire (for autoimmune regulator), which regulates the expression of some 300 to 1,000 antigens in the thymus. Humans and mice lacking the normal Aire gene suffer from multiple autoimmune diseases including diseases that target the thyroid, adrenal, ovary, and eye.

In 2002, Anderson, then at Harvard Medical School, and colleagues there demonstrated that knocking out the Aire gene in the mouse thymus led to failures of expression of a number of genes in peripheral tissues, resulting in autoimmune diseases in those tissues -- the first direct evidence linking gene knockouts in the thymus to autoimmune defects in body tissues. The study, however, did not link a specific organ autoimmune attack with a specific protein missing in the thymus.

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Source:University of California - San Francisco


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