Immune system pathway identified to fight allergens, asthma

Role of genetic components of dendritic cells could lead to more effective drugs, University of Pittsburgh School of Medicine study says

PITTSBURGH, May 7 – For the first time, researchers from the University of Pittsburgh School of Medicine have identified genetic components of dendritic cells that are key to asthma and allergy-related immune response malfunction. Targeting these elements could result in more effective drugs to treat allergic disorders and asthma, according to a study reported in the May edition of the journal Nature Medicine.

Dendritic cells are vital to immune response in that they recognize, capture and introduce threatening organisms to T lymphocytes¯other immune cells that secrete potent proteins called cytokines that surround and destroy the invaders. However, the Pittsburgh team’s study goes further to illuminate a pathway that allergens use to act directly on dendritic cells to propel differentiation into the T lymphocytes that fight back.

“We now have identified a molecule, c-Kit, that is central to the process of allergic response,” said Anuradha Ray, Ph.D., co-corresponding author and professor of medicine and immunology in the Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine. “We show that genes encoding for c-Kit and the cytokine interleukin 6 (IL-6) are significantly activated when allergens are present, but c-Kit is the very first molecule that gets triggered.”

Interactions between viruses and bacteria and molecular steps that initiate the immune defense have remained largely unknown. Using cells cultured from c-Kit mutant mice, Dr. Ray, her husband and co-corresponding author Prabir Ray, Ph.D., and their colleagues studied molecular reactions to assaults by cholera toxin and a standard allergen, house dust mites. In addition to c-Kit and IL-6, they found effects on stem cell factor and Jagged-2¯immune system molecules that are parts of the activation process.