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 predominantly Th-2 associated cytokines such as IL-4, and IL-5. We are particularly interested in characterizing cytokines that may act to downmodulate the earliest phases of the allergic response including IL-10. This project seeks to use a number of diffferent gene disrupted or """"""""knockout"""""""" cytokine mice (e.g. IL-10ko, IL-12ko, IL-5ko etc.) to examine the events responsible for immediate cytokine production in the mucosal environment upon allergen challenge, including possible production by mast cells, and how cytokines such as IL-10 can help modulate this early response. In particular, we have seen an important role for IL-10 in influencing mast cell stability, something that may prove essential to the prevention both the early stages of allergic responses, including histamine release, and the later phases of allergic disease involving allergic inflammation and influx of eosinophils and other mediators of the allergic phenomenon.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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Lippert, Eric; Yowe, David L; Gonzalo, Jose-Angel et al. (2003) Role of regulator of G protein signaling 16 in inflammation-induced T lymphocyte migration and activation. J Immunol 171:1542-55
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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
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