Critical Autoimmune Regulator Identified in the Thymus

Researchers studying the transcription factor aire (autoimmune regulator) found that humans expressing a defective form of aire develop multi-organ autoimmune disease, showing that it plays a critical role in the development of immune system tolerance for self-antigens. This finding was published in the October 11, 2002, online edition of Science.

The aire protein appears to work by stimulating the production in the thymus of a wide array of proteins from the body's periphery. These peripheral proteins serve to "teach” T cells which proteins to recognize and avoid.

To study the action of aire, the investigators from Harvard Medical School (Boston, MA, USA) developed a mouse line that lacked the gene for aire production. Mutant mice lacking aire exhibited in their thymus only a fraction of the peripheral self-proteins found in the thymus of normal mice, and the mutants exhibited widespread autoimmunity. The condition seen in the mice was reminiscent of a condition found in humans carrying a defective AIRE gene, called autoimmune polyglandular syndrome.

"Our findings lead back to humans because they tell us about a very important mechanism for controlling autoimmunity, said senior author Dr. Diane Mathis, professor of medicine at Harvard Medical School. "At the same time, they may help us understand why people develop autoimmune diseases.”




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