Allergic asthma is thought to stem from inappropriate immune responses to inhaled antigens. Therefore, to prevent or treat allergic asthma, it is important to identify the cellular and molecular mechanisms that initially give rise to allergic sensitization. Accordingly, our laboratory uses mouse models of asthma to study allergic sensitization through the airway. To do this, we sensitize mice to ovalbumin by delivering this protein to the airway together with low levels of lipopolysaccharide (LPS). Pulmonary dendritic cells that line the airway epithelium take up this antigen and migrate to draining thoracic lymph nodes to present OVA-derived peptides to nave T cells. We have found that this method of sensitization primes a qualitatively different type of immune response than the more conventional method of sensitization involving intraperitoneal (i.p.) injections of OVA complexed with aluminum hydroxide (alum). Thus, sensitization through the airway, but not through the peritoneum, induces robust T helper (Th)17 responses. These Th17 cells produce IL-17 upon challenge with OVA that in turn leads to airway neutrophilia and airway hyperresponsiveness (AHR). Ongoing Th17 responses to inhaled allergens might therefore distinguish severe asthma from less serious Th2-mediated diseases of the airway.? ? In addition to studying the mechanisms underlying the induction of Th17 cells in the lung, we also study the impact of various environmental pollutants on pulmonary dendritic cell activation, and how these pollutants can act as adjuvants in the lung to promote allergic sensitization through the airway.? ? The molecules that direct homing of antigen-specific T cells to the lung have not been identified. We seek to identify these molecules by culturing pulmonary dendritic cells with OVA-specific T cells from OT-II mice.? ? Pulmonary dendritic cells are thought to arise from monocytes that arrive in the lung from the blood. Although the chemokine receptors, CCR2 and CX3CR1 have both been implicated in the recruitment of monocytes to the lung, it is still unclear whether monocytes displaying these two molecules give rise to pulmonary dendritic cells having different functional properties. One of the projects in our laboratory is directed at identifying such differences.
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