Mucosal Immunology and Asthma
We are interested in how the lung’s immune system responds to inhaled particles, allergens and viruses, and how this process breaks down in asthma leading to deleterious immune responses that cause allergic airway inflammation. We currently compartmentalize immunity into innate vs. adaptive components. The innate immune system is made up of frontline sentinels (e.g. epithelial cells, dendritic cells, etc.) that sense and respond to molecular patterns encoded by pathogens or released by injured cells. Activated innate immune cells then recruit and activate professional lymphocytes such as B and T cells, which comprise the adaptive immune system. Adaptive immune cells have two key properties. First, they express an enormously diverse repertoire of antigen specific receptors. Second, they can differentiate into long-lived memory cells. The compartmentalization of immune responses into innate vs. adaptive components is a useful construct, and positions innate immune cells at the host-environment interface.
Inhaled allergens and particles are generally harmless, and are cleared from the respiratory tract by numerous defense mechanisms. For reasons that are not clear, these defenses break down in subjects with asthma, resulting in deleterious immune responses that lead to tissue inflammation. Many pathologic immune responses in asthma are “type 2”, that is they are characterized by aberrant production of the Th2-type cytokines IL-4, IL-5 and IL-13 by CD4+ T cells and innate lymphoid cells. I began my career by studying the molecular regulation of Th2 gene expression in lymphocytes. Currently a major emphasis of my lab is to study the cross-talk between the innate and adaptive immune systems that leads to pathologic type 2 immune responses. We use in vitro co-cultures of relevant cell types, as well as mouse models of asthma emphasizing mucosal routes of sensitization. I am also a practicing physician and see outpatients with severe asthma at the Mary Parkes Asthma Center. I direct the Study of Asthma in Rochester (SOAR). In SOAR1, we established a biobank of samples from more than 200 subjects with varying degrees of asthma severity. In SOAR2, we are prospectively enrolling asthmatics at time of exacerbation in a longitudinal follow-up study.