Our laboratory has developed mouse models of allergic eye disease and asthma to enable us to study the pathogenesis of allergic disease in vivo. Our model of allergic conjunctivitis allows us to use topical application of allergens to assess a localized allergic response, and is particularly useful for examining goblet cell hyperproliferation and mast cell degranulation. Our models of allergen-induced airway hyperresponsiveness, mimic many of the aspects of human asthma, and are useful for studying systemic allergic responses. These models allow us to examine airway changes due to allergic inflammation, edema, and smooth muscle contractility. A number of studies have suggested that after allergen exposure, IgE bearing cells, such as mast cells and basophils, are first activiated. Later, other cells such as T lymphocytes enter the airways, are activated by allergen, and play a key role in regulating this inflammatory response through the elaboration of cytokines such as IL-4, IL-5, and IFN-gamma. This project seeks to use a number of diffferent gene disrupted or """"""""knockout"""""""" mice (e.g. IgE receptor gamma chain ko, IL-21 ko, complement factor ko) to examine the events responsible for immediate cytokine production in the mucosal environment upon allergen challenge, including possible production by mast cells, basophils, and neutrophils. In particular we have seen an important role for basophils in early IL-4 production, something that is essential to the development of asthma and other allergic diseases.
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|Bundoc, Virgilio G; Keane-Myers, Andrea (2003) Animal models of ocular allergy. Curr Opin Allergy Clin Immunol 3:375-9|
|Luccioli, Stefano; Brody, Dan T; Hasan, Syed et al. (2002) IgE(+), Kit(-), I-A/I-E(-) myeloid cells are the initial source of Il-4 after antigen challenge in a mouse model of allergic pulmonary inflammation. J Allergy Clin Immunol 110:117-24|
|Keane-Myers, A (2001) The pathogenesis of allergic conjunctivitis. Curr Allergy Asthma Rep 1:550-7|
|Kunert, K S; Keane-Myers, A M; Spurr-Michaud, S et al. (2001) Alteration in goblet cell numbers and mucin gene expression in a mouse model of allergic conjunctivitis. Invest Ophthalmol Vis Sci 42:2483-9|
|Casolaro, V; Keane-Myers, A M; Swendeman, S L et al. (2000) Identification and characterization of a critical CP2-binding element in the human interleukin-4 promoter. J Biol Chem 275:36605-11|