Miranda Curtiss, M.D., Ph.D.

Miranda Curtiss, M.D., Ph.D.

Institution: University of Alabama at Birmingham

Project: CXCR5/Chi3l1 axis regulates allergic disease

Grant(s): Allergic Respiratory Diseases Award

Allergic diseases are becoming increasingly prevalent in the United States. Although we have developed new drugs to control asthma, we are still learning about the underlying mechanisms that cause this disease. Using genetic approaches from parasitic infections that cause similar immune system activation to allergic disease, we have identified genes that are important in the interactions between the cells that initiate and maintain allergic inflammation (dendritic cells) and the effector cells that cause inflammatory damage during allergic reactions (T cells). We will extend our studies from parasitic infections into mouse models of allergic asthma to test the roles of these genes. Both the parasitic infection and our asthma model contain chitin, a carbohydrate found in pathogens and allergens, and one of our target genes is a chitin-binding protein. We can explore how our protective immune responses to chitin may influence our allergic reactions in asthma.

Update: Using a mouse model of asthma triggered by the mold Aspergillus fumigatus, we focused our attention to CD4 T cells, which are known to produce cytokines critical in asthma (these include IL-4, IL-5 and IL-13 targets for monoclonal antibodies used to treat asthma patients). We characterized CD4 T cells recruited to lung draining lymph nodes and found that the majority of IL-4 producing CD4 T cells express surface markers of T follicular helper cells (TFH). IL-4 producing TFH cells are critical in generating IgE antibody, which is a defining feature of allergic disease (another monoclonal antibody treatment used for asthma patients recognizes IgE). Chi3l1 deficient mice respond with fewer TFH cells in the lung draining lymph nodes during the Aspergillus asthma model, and they also have less inflammatory cells in their airways.

Funded in partnership with the American Academy of Allergy, Asthma & Immunology

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