Mouse models of allergic diseases

Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA.
Current opinion in immunology (Impact Factor: 7.48). 10/2009; 21(6):660-5. DOI: 10.1016/j.coi.2009.09.005
Source: PubMed


The increasing prevalence of allergic diseases worldwide is posing significant socio-economic challenges. The pathogenesis of these diseases reflects a complex interaction of genetic and environmental factors. The heterogeneity of disease phenotypes challenges the concept of single mechanisms of disease. As human experimentation is limited, animal models have been developed to provide insights into pathogenesis and potential for discovery of novel therapeutics. Mice have served in models of many of the allergic diseases including asthma, allergic rhinitis, food allergy, atopic dermatitis (AD), and allergic conjunctivitis. Although much has been learned from these investigations, there are limitations when these models are translated to the human diseases.

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    • "The NC/Nga mouse is the first reported spontaneously occurring AD model [14], [15]. Skin changes that closely mimic human AD are induced in NC/Nga mice following exposure to various environmental aeroallergens [14]. "
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    ABSTRACT: Atopic dermatitis (AD) is characterized by chronic highly pruritic and relapsing inflammatory skin lesions. Despite its growing prevalence, therapeutic treatments remain limited. Natural immune modulators from herbal extracts or derivatives may be useful for treating AD symptoms. This study examined the effect of 7,8,4'-trihydroxyisoflavone (7,8,4'-THIF), a metabolite of soy isoflavone daidzin, on AD-like symptoms. Repeated epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) was performed on the ear and dorsal skin of NC/Nga mice to induce AD-like symptoms and skin lesions, and 7,8,4'-THIF (200 and 400 nmol) or tacrolimus (100 µg) was applied topically for 3 weeks to assess their anti-pruritic effects. We found that 7,8,4'-THIF alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness, and scratching behavior. Histopathological analysis demonstrated that 7,8,4'-THIF decreased DNCB-induced eosinophil and mast cell infiltration into skin lesions. We also found that 7,8,4'-THIF significantly alleviated DNCB-induced loss of water through the epidermal layer. In addition to reducing the DNCB-induced increase in serum IgE, 7,8,4'-THIF also lowered skin lesion levels of the chemokine thymus and activation regulated chemokine; Th2 cytokines interleukin (IL)-4, IL-5, and IL-13; and Th1 cytokines IL-12 and interferon-γ. These results suggest that 7,8,4'-THIF might be a potential therapeutic candidate for the treatment of atopic dermatitis.
    PLoS ONE 08/2014; 9(8):e104938. DOI:10.1371/journal.pone.0104938 · 3.23 Impact Factor
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    • "Functionally, this model is divided in two phases, ie, sensitization and provocation.26,27 In the sensitization phase, the experimental allergen, ie, ovalbumin, is taken up by dendritic cells that induce a polarized Th2 response and IgE production. "
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    ABSTRACT: Histamine is an important mediator in the development of allergic reactions. The biological effects of histamine are mediated through four histaminergic receptors. In recent years, an important role has been assigned to the proinflammatory functions of histamine regarding the H4 receptor. Previously, we have demonstrated that injection of immature dendritic cells treated with histamine into allergic mice promotes an increase in CD8(+) Tc2 lymphocytes, which are involved in the worsening of allergy symptoms during the chronic phase of the disease. The aim of this study was to evaluate the role of the H3/H4 receptor antagonist, thioperamide, in allergy. Ovalbumin-allergized mice and nonallergized mice were injected with phosphate-buffered saline, dendritic cells, or thioperamide-treated dendritic cells. After treatment, the lungs of the mice were obtained and analyzed for changes in the populations of dendritic cells and T lymphocytes, as well as the expression of H and H4 receptors in mononuclear lung cells. We found an increase in regulatory T cells in the lungs of allergic mice intratracheally injected with dendritic cells which had their H3/H4 receptors blocked with thioperamide. We also found an increase in the production of interleukin-10 by dendritic cells of the lung. Finally, we observed a decrease in serum levels of specific anti-IgE and a reduction of eosinophils in bronchoalveolar lavage from allergic mice. Thioperamide induces a significant improvement in symptoms of allergic reaction perhaps via induction of regulatory T lymphocytes. These findings may become relevant in the understanding of type 1 hypersensivity reactions.
    Journal of Asthma and Allergy 09/2011; 4:93-102. DOI:10.2147/JAA.S23507
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    • "In these models, different strains of mice (with different susceptibilities) can be used. In addition, the mode of sensitization (with or without adjuvant), the route of sensitization (systemic or local airway sensitization), and the frequency and duration of airway allergen challenge can be varied, leading to identification of various pathways and mechanisms that perhaps reflect the heterogeneity of human asthma [20, 21]. "
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    ABSTRACT: Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract diseases (bronchiolitis and pneumonia) during infancy and early childhood. There is increasing evidence which indicates that severe pulmonary disease caused by RSV infection in infancy is associated with recurrent wheezing and development of asthma later in childhood. However, the underlying mechanisms linking RSV infection to persistent airway hyperresponsiveness and dysfunction are not fully defined. To study these processes in ways which are not available in humans, animal models have been established and have provided valuable insight into the pathophysiology of RSV-induced disease. In this paper, we discuss experimental models of RSV infection in mice and highlight a new investigative approach in which mice are initially infected as neonates and then reinfected later in life. The findings shed light on the mechanisms underlying the association between early severe RSV infection and development of asthma later in childhood.
    Pulmonary Medicine 07/2011; 2011(6):748038. DOI:10.1155/2011/748038
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