5 research outputs found

    Mast Cells Are Required for Full Expression of Allergen/SEB-Induced Skin Inflammation

    Get PDF
    Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B–induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ−/- or Rag1−/-). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcεRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD

    Immunological and Molecular Bases of Epidermal Symptoms of Atopic Dermatitis in PLC[Beta]3-/- Model /

    No full text
    Atopic dermatitis (AD) is a chronic inflammatory disease, characterized by eczematous lesion (skin inflammation with serous discharge) and excessive pruritus(itching). The early onset, relapsing nature and worsening of scratch- itch symptoms at night results in both patients' restlessness and socioeconomic burden. In addition to the prominent skin symptoms, AD patients are prone to develop allergic rhinitis (nasal allergy) and asthma, through a progressive hypersensitization process called atopic march. Moreover, the impaired skin barrier function in AD patients makes them vulnerable for infection by microbial organisms, which can further exacerbate the inflammation of the skin. Both environmental and genetic factors contribute to development of AD. However the exact cause of this disease is still unknown. Studies aimed at identifying the causes of AD have led to the development of multiple murine models of this disease. Observations of these models have given rise to treatments that ease AD's symptoms, but the lack of a permanent cure and the high ratio of deleterious side effects to symptom suppression necessitate the search for novel pathways that can be targeted for long lasting treatment. We analyzed the epidermis of a new mouse model in which the lack of a functional gene for PLC[Beta]3 leads to spontaneous AD. Upon challenging the skin with extracts of house dust mite, Dermatophagoides farina (Der f), and Staphylococcal enterotoxin B (SEB), mice exhibited early onset AD symptoms. These symptoms appeared more severe in PLC[Beta]3-/- mice compared to their wild-type littermates. By using these inducible AD models, we characterized the impact of immune cells and their downstream effectors on the epidermal phenotypes of atopic dermatiti

    Critical Role for Mast Cell Stat5 Activity in Skin Inflammation

    Get PDF
    Atopic dermatitis (AD) is a chronic inflammatory skin disease. Here, we show that phospholipase C-β3 (PLC-β3)-deficient mice spontaneously develop AD-like skin lesions and more severe allergen-induced dermatitis than wild-type mice. Mast cells were required for both AD models and remarkably increased in the skin of Plcb3−/− mice because of the increased Stat5 and reduced SHP-1 activities. Mast cell-specific deletion of Stat5 gene ameliorated allergen-induced dermatitis, whereas that of Shp1 gene encoding Stat5-inactivating SHP-1 exacerbated it. PLC-β3 regulates the expression of periostin in fibroblasts and TSLP in keratinocytes, two proteins critically involved in AD pathogenesis. Furthermore, polymorphisms in PLCB3, SHP1, STAT5A, and STAT5B genes were associated with human AD. Mast cell expression of PLC-β3 was inversely correlated with that of phospho-STAT5, and increased mast cells with high levels of phospho-STAT5 were found in lesional skin of some AD patients. Therefore, STAT5 regulatory mechanisms in mast cells are important for AD pathogenesis
    corecore