Welcome to the Allergic Disease and Antiviral Responses Program at UT Southwestern Medical Center

Our goal is to understand the complex interaction between viral infections and allergic diseases

More Understanding, Better Healing

In a collaborative effort, Dr. David Farrar and Dr. Michelle Gill have uncovered an important reciprocal negative regulatory pathway that may shed light on the devastating effects of viral infections on allergic diseases, such as allergic asthma. In response to viral infections, innate cells of the immune system, called dendritic cells, secrete the antiviral cytokine, type I interferon (IFN-α/β). This cytokine is critical in suppressing viral replication and spread to other cells. In turn, dendritic cells prime populations of T cells to combat the virus by secreting inflammatory cytokines and by providing help to B cells to produce antibody. This is the normal pathway that the immune system takes to combat viral infections.

During allergic responses, T cells become primed to normally innocuous substances such as pollens, dust, and pet dander, just to name a few. These aberrant T cells, called Th2 cells, drive the production of a highly inflammatory antibody type called IgE, which is the main mediator of inflammation in allergic diseases. In our recent studies, we found that IFN-α/β, secreted during viral infections, blocks the development of Th2 cells and can prevent them from secreting inflammatory cytokines. Conversely, the product of the Th2 pathway, IgE, blocks the secretion of IFN-α/β from dendritic cells responding to viral infections.

Thus, the very innate cytokine that blocks the development of allergic T cells is suppressed by IgE-mediated allergic stimulation. Consequently, this pathway could reinforce priming of allergic T cells through viral infections, which we propose is most relevant during the initial stages of atopy induction as well as in cases of viral exacerbations of allergic asthma. These discoveries raise some very important questions. First, can IFN-α/β destabilize and suppress the activity of allergen-specific Th2 cells? If so, then we propose that either direct treatment with IFN-α/β or an upstream inducer of IFN-α/β secretion could be used to treat allergic conditions. However, if IFN-α/β cannot reverse the Th2 phenotype in T cells from atopic individuals, then understanding the molecular lesion in these cells would provide clues to the initial priming events and genetic contributions that lead to the allergic state. Second, what is the mechanism underlying the suppression of IFN-α/β by allergic stimulation, and can viral-induced IFN-α/β responses from innate cells be restored in allergic individuals? The Allergic Disease and Antiviral Response Programs seeks to answer these important questions with the ultimate goal of uncovering new avenues for therapeutic interventions for allergic diseases.