Research Projects
Led by Dr. Kita, the Allergic Diseases Lab has several research projects aimed at better understanding the process behind many common allergic diseases and conditions.
Eosinophil biology
We're investigating the regulatory and molecular mechanisms of eosinophil activation. By using isolated human eosinophils and various in vitro models, we identified the biological and pharmacological stimuli involved in eosinophil activation. We investigated how eosinophil function is regulated by cell surface receptors and adhesion molecules, their ligands, and intracellular signaling pathways. Animal models also were used to evaluate the physiologic significance of these in vitro observations.
This body of work helped improve understanding of the immunological mechanisms of eosinophil activation and effector functions.
Mechanisms of chronic sinusitis
Our team is studying the role of eosinophils in disease and the immunological mechanisms of eosinophilic inflammation in mucosal organs. These diseases include asthma, eosinophilic esophagitis and chronic sinusitis with nasal polyps. In particular, our team has spent considerable effort investigating the etiology and immunologic mechanisms of chronic sinusitis and testing a hypothesis that environmental fungi are involved in the pathophysiology of this disease.
This body of work contributed to an appreciation of the presence of extensive eosinophilic inflammation and degranulation in certain diseases. It also led to the recognition that fungus may play a role in some types of chronic sinusitis.
Environmental allergens
Our lab is working to better define the mechanisms of Th2-type immune responses. We're investigating how natural allergens interact with immune and inflammatory cells in the mucosal surface and how they activate the innate and adaptive immune systems. These natural allergens include fungi, house dust mites and food allergens.
Key findings are that natural allergens are not inert proteins but have immunostimulatory activities that are derived from proteases and carbohydrates within the allergens. These molecules activate airway epithelial cells, dendritic cells and eosinophils through unique receptors or by engaging endogenous damage associated molecule patterns. We also discovered that CD4+ T cells with unique biological features, such as those stimulating B cells to produce IgE antibodies and those resident in mucosal tissues for a prolonged period, play important roles in allergic diseases.
This body of work contributed to the recognition of immunological activities of allergens and the importance of CD4+ T cells, which likely serve to sensitize people or worsen the disease process.
Airway exposure
Using in vitro systems and mouse models, we're studying how airway exposure to common allergens leads to development of Th2-type immunity. Epithelial cell-derived cytokines, in particular IL-33 and thymic stromal lymphopoietin, played important roles in linking the innate and adaptive immune systems in the airways and in promoting Th2-type immune responses and inflammation. These molecules also are likely important in chronic airway inflammation and remodeling. The ATP-mediated stress responses also likely play key roles in triggering IL-33 secretion by airway epithelial cells.
These studies demonstrated the importance of epithelial-derived cytokines to initiate and modulate Th2-type immune responses.
Immunobiology of innate lymphoid cells
During our study on the effects of natural allergens on airway epithelium, we found that type 2 cytokines, such as IL-5 and IL-13, are produced by innate immune responses, even in the absence of T cells or B cells. These studies led to the identification of a novel immune cell that is now designated by a consensus report as group 2 innate lymphoid cells (ILC2s). ILC2s also were identified and found to be increased in peripheral blood of people with asthma.
This body of work contributed conceptual advances in the field to recognize the presence of the innate arm of type 2 immunity in airway mucosa. This work also promoted subsequent clinical studies to investigate the role of ILC2s in disease.