Misplaced DNA generates problems.

Autoimmune diseases largely remain a mystery. Infections or injuries often precede autoimmune attacks, but how can those events make the body attack its own tissues?

Misplaced DNA inside cells may lead them to rally the immune system to destroy normal tissues, suggests Leonard D. Kohn of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. In the March 2 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, he and his colleagues show that introducing DNA into a cell's cytoplasm--rather than the nucleus, where most genetic material resides--triggers changes that scientists had overlooked.

In response to the added DNA, the cell turns on genes usually employed only by specialty cells that display targets for the immune system to attack. Since viruses often introduce their DNA into a cell's cytoplasm, and damaged cells may have their DNA leak out of the nucleus, Kohn's finding may explain why infections and tissue injuries are associated with autoimmunity.

The results may also indicate why gene therapy has had little success. Viruses are often used to deliver the genes to the cytoplasm, and frequently the immune system later destroys the cells that have received the DNA. Scientists are studying compounds that may suppress the changes brought about by DNA in the cytoplasm, says Kohn.