Asthma, genes, environment and the "hygiene hypothesis"
Asthma now affects about 10 percent of U.S. children. It's caused by both genetic and environmental factors, including allergens, air pollution and infections. However, some studies suggest that infections and "dirty" environments can actually protect people against asthma by stimulating the immune system in a particular way, an idea known as the hygiene hypothesis. But no one has fully explained the hygiene connection, or what specific infections might be involved. And while many genes have some association with asthma, finding specific asthma susceptibility genes has been difficult.
Dale Umetsu, MD, PhD, and Rosemarie DeKruyff, PhD, recently relocated to Children's Hospital Boston's Division of Immunology from Stanford University, and have been on a research journey that may yield a biological explanation for the hygiene hypothesis—and possibly an approach to preventing asthma. In 2001, they reported discovering TIM, a family of genes that strongly affects asthma susceptibility in mice. They later identified a human counterpart called TIM-1 that protects against asthma and other allergic diseases, but only in people with prior hepatitis A infection. Since hepatitis A spreads through fecal contact, it was thought to be an indicator of a "dirty" environment. Its prevalence has fallen markedly in Western countries since the 1960s—while asthma prevalence has risen dramatically.
But how can a viral infection protect people from allergies and asthma? Interestingly, TIM-1 turns out to be the receptor that hepatitis A uses to infect human cells. In the May Nature Immunology, DeKruyff and Umetsu showed that stimulating the TIM-1 receptor artificially can change the immune system in a way that protects against asthma. A better understanding of these changes may lead to a way of "immunizing" people against asthma by mimicking hepatitis A infection.