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He R, Kim HY, Yoon J et al.Exaggerated IL-17 response to epicutaneous sensitization mediates airway inflammation in the absence of IL-4 and IL-13. J Allergy Clin Immunol 124:761-770

Division of Immunology, Children's Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, Mass., USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 10/2009; 124(4):761-70.e1. DOI: 10.1016/j.jaci.2009.07.040
Source: PubMed

ABSTRACT Atopic dermatitis (AD) is characterized by local and systemic T(H)2 responses to cutaneously introduced allergens and is a risk factor for asthma. Blockade of T(H)2 cytokines has been suggested as therapy for AD.
We sought to examine the effect of the absence of IL-4 and IL-13 on the T(H)17 response to epicutaneous sensitization in a murine model of allergic skin inflammation with features of AD.
Wild-type, IL4 knockout (KO), IL13 KO and IL4/13 double KO (DKO) mice were subjected to epicutaneous sensitization with ovalbumin (OVA) or saline and airway challenged with OVA. Systemic immune responses to OVA, skin and airway inflammation, and airway hyperresponsiveness were examined.
OVA-sensitized DKO mice exhibited impaired T(H)2-driven responses with undetectable OVA-specific IgE levels and severely diminished eosinophil infiltration at sensitized skin sites but intact dermal infiltration with CD4(+) cells. DKO mice mounted exaggerated IL-17A but normal IFN-gamma and IL-5 systemic responses. Airway challenge of these mice with OVA caused marked upregulation of IL-17 mRNA expression in the lungs, increased neutrophilia in bronchoalveolar lavage fluid, airway inflammation characterized by mononuclear cell infiltration with no detectable eosinophils, and bronchial hyperresponsiveness to methacholine that were reversed by IL-17 blockade. IL-4, but not IL-13, was identified as the major T(H)2 cytokine that downregulates the IL-17 response in epicutaneously sensitized mice.
Epicutaneous sensitization in the absence of IL-4/IL-13 induces an exaggerated T(H)17 response systemically and in lungs after antigen challenge that results in airway inflammation and airway hyperresponsiveness.

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    • "It thus is possible that patients become sensitized towards Der p 11 and other mite body-associated allergens by skin contact. In this context it has been found that epicutaneous sensitization to protein antigens indeed can induce allergic sensitization and even may enhance subsequent respiratory allergy towards the same antigen (Beck and Leung, 2000; He et al., 2009; Spergel et al., 1998). In an experimental dog model of acute atopic dermatitis, epicutaneous application of HDM extracts destroyed the skin barrier function by reduction of stratum corneum ceramides (Stahl et al., 2012). "
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    ABSTRACT: House dust mites belong to the most potent indoor allergen sources worldwide and are associated with allergic manifestations in the respiratory tract and the skin. Here we studied the importance of the high molecular weight allergen, Der p 11, in HDM allergy. Sequence analysis showed that Der p 11 has high homology to paramyosins from mites, ticks and other invertebrates. A synthetic gene coding for Der p 11 was expressed in Escherichia coli and rDer p 11 purified to homogeneity as folded, alpha helical protein as determined by circular dichroism spectroscopy. Using antibodies raised against rDer p 11 and immunogold electron microscopy, the allergen was localized in the muscle beneath the skin of mite bodies but not in faeces. IgE reactivity of rDer p 11 was tested with sera from HDM allergic patients from Europe and Africa in RAST-based dot-blot assays. Interestingly, we found that Der p 11 is a major allergen for patients suffering from atopic dermatitis (AD), whereas it is only a minor allergen for patients suffering from respiratory forms of HDM allergy. Thus, rDer p 11 might be a useful serological marker allergen for the identification of a subgroup of HDM allergic patients suffering from HDM-associated AD.Journal of Investigative Dermatology accepted article preview online, 07 July 2014; doi:10.1038/jid.2014.271.
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    • "Recently, the conceptual focus on understanding AD has increasingly shifted to including a primary defect in the epithelial barrier as an initial event in the atopic march. Many studies in animal models demonstrate that epidermal barrier dysfunction can be caused by repeated sensitization to allergens to the skin, which leads to phenotypes of atopic dermatitis, systemic sensitization, increased risk of allergic rhinitis, lung inflammation and AHR910. "
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