The Immunogenetics Group conducts several ongoing research projects within the Laboratory of Respiratory Biology.
Bacterial product-mediated allergic sensitization through the airway
We recently showed that the bacterial product, flagellin, is present in common house dust and potently promotes allergic sensitization to common indoor allergens. Like lipopolysaccharide (LPS), flagellin activates the innate immune system, which in turn promotes T helper (Th)2 and Th17 cell development. Whereas Th2 responses are critical for eosinophil accumulation in the airway, Th17 responses are responsible for neutrophil recruitment. Both Th2 and Th17 responses are required for the development of airway hyperresponsiveness (AHR), a salient feature of asthma. Current studies are aimed at understanding the molecular mechanisms that underlying bacterial product-mediated allergic sensitization through the airway.
The roles of pulmonary dendritic cell subsets in the initiation of allergic responses to inhaled antigens
Dendritic cells (DCs) are highly efficient antigen-presenting cells that reside in many organs, including the epithelial lining of the lung. DCs are critical for the initiation of some allergic responses, as well as for their maintenance in the context of continued allergen challenge. We recently showed that allergic responses to inhaled allergens are primarily directed by a subset of lung DCs that express the cell surface marker, CD103. These cells express high levels of the chemokine receptor, CCR7, and efficiently migrate to draining lymph nodes. By contrast, lung DCs derived from monocytes (moDCs) lack CCR7 and are non-migratory. Ongoing studies in the lab seek to understand the function of these non-migratory lung DCs.
The cellular and molecular mechanisms that control or regulate ongoing allergic pulmonary inflammation
Although LPS can promote allergic sensitization, some studies have shown that exposure to this bacterial product can protect against developing asthma. We have developed an animal model to study this. Mice instilled through the airway with ovalbumin (OVA) plus LPS develop acute allergic responses to a single subsequent challenge with aerosolized OVA. However, continued daily challenges with OVA suppress those allergic responses in a manner dependent on ICOS and Ebi3, a subunit of IL-35. The Immunogenetics lab seeks to gain a more complete understanding of the cellular and molecular basis of this suppression because of its potential to reveal novel targets in the treatment of established asthma.