Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis

Nomura, Ichiro; Gao, Bifeng; Boguniewicz, Mark; Darst, Marc A.; Travers, Jeffrey B.; Leung, Donald Y.M.

doi:10.1016/j.jaci.2003.08.049

Cited by 309 publications

(93 citation statements)

References 44 publications

(56 reference statements)

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“…Representative molecules which are differentially expressed in AE patients found in the transcriptome research are shown in the boxes. Transcripts differentially expressed in skin lesion [30], peripheral blood monocytes [19], CD4+ T cells [10,11,12,13, 16] and eosinophils [28] derived from AE patients are summarized. PAMPs = Pathogen-associated molecular patterns; SEB = staphylococcal enterotoxin-B; PAFR = platelet-activating factor receptor; explanations of other abbreviations are provided in table 1. …”

Section: Resultsmentioning

confidence: 99%

“…Indeed, Genox faced the difficulty in determining whether the upregulated genes in the skin are truly upregulated in the skin-dwelling cells or artifactually upregulated by the contamination of inflammatory cells. Nomura et al [30] have succeeded in solving this problem in their microarray study on AE skin specimens by comparing the tissues derived from AE and psoriasis. They identified several genes for chemoattractant cytokines and chemokines, which play a central role in defining the nature of the inflammatory infiltrate in AE, to be differentially expressed.…”

Section: Differentially Expressed Genes In Skin Lesionmentioning

confidence: 99%

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Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema

Saito

2005

Int Arch Allergy Immunol

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Background: Atopic eczema (AE) is a chronic inflammatory skin disorder with an increasing prevalence in industrialized countries. Methods: Genox Research Incorporation was founded in 1996 to identify new genes involved in allergic diseases in collaboration with the National Children’s Hospital in Tokyo. In the AE project, they have discovered several hundred new genes and partial DNA sequences by mainly using microarrays. Here, I review the results obtained using transcriptome analysis, performed by Genox and other investigators. Results:Transcriptome analysis using skin lesion, CD4+ T cells, monocytes and eosinophils derived from AE patients identified some differentially expressed genes which became biologically relevant in the following studies. Missing linkages between these genes have been found due to the recent development of genomics. Conclusion:Many AE-related genes found in the genome-wide studies still remain to be determined regarding their functions and to be systemically organized. After the comprehensive characterization of these genes by further studies, we will identify the precise molecular mechanisms involved in AE and other diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Differentially Expressed Genes In Skin Lesionmentioning

confidence: 99%

Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema

Saito

2005

Int Arch Allergy Immunol

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“…Differ- ential handling of S. aureus may influence the likelihood of subsequent development of a disease-relevant allergen-specific immune response. Recent data suggest that cutaneous expression of antimicrobial peptides/proteins may influence disease, and indeed altered defensin expression in lesional AD skin has been documented (30,31). Furthermore, AD has been linked to a region of chromosome 1 that contains numerous genes thought to encode antimicrobial proteins (32).…”

Section: Discussionmentioning

confidence: 99%

Bacterial superantigen facilitates epithelial presentation of allergen to T helper 2 cells

Ardern‐Jones

Black

Bateman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Although clinical and laboratory evidence support roles for both staphylococcal infection and environmental allergens in the pathogenesis of atopic dermatitis, human studies have largely considered these variables independently. We sought to test the hypothesis that staphylococcal superantigen influences the allergen-specific T cell response. We first mapped a Der p 1 epitope and used HLA DRB1*1501 class II tetramer-based cell sorted populations to show that specific CD4 ؉ T cells were able to recognize the peptide presented by HLA DR-matched keratinocytes. We observed that staphylococcal enterotoxin B (SEB) enhanced the IL-4 Der p 1-specific T cell response. This response was mediated by two synergistic mechanisms: first, SEB-induced IFN-␥ promoted class II and intercellular adhesion molecule-1 expression by presenting keratinocytes; and second, SEB-induced IL-4 directly amplified allergen-specific CD4 ؉ T cell production of many cytokines. We propose that handling of staphylococcal infection is a critical step in the amplification of the allergen-specific T cell response, linking two common disease associations and with implications for the prevention and treatment of atopic disease.T here is convincing evidence that allergic reactivity to environmental challenge has a role in the pathogenesis of atopic dermatitis (AD). For example, the histology of AD shares many features with classic allergic contact delayed-type hypersensitivity, including spongiosis and a dominant T cell inflammatory infiltrate that is distributed predominantly in a dermal, and to a lesser extent epidermal pattern. Approximately 80% of individuals with AD have circulating specific IgE recognizing one or more of house dust mite, cat, dog, grass, and other ubiquitous environmental allergens (1). In many studies, allergen-specific CD4 ϩ and CD8 ϩ T cells have been documented to be present in the peripheral blood and lesional skin of affected individuals and to produce diverse cytokines but with a frequent T helper 2 (Th2) dominance (2, 3). House dust mite extract application to the skin of individuals with AD can reproduce eczematous changes (4, 5), and allergen avoidance has been shown by some to be partially effective (6, 7). Keratinocytes have been shown to up-regulate HLA class II and intercellular adhesion molecule-1 (ICAM-1) in AD and other inflammatory dermatoses (8, 9) and also in response to injection of IFN-␥ into normal skin (10). However, in isolation, allergic reactivity to an environmental challenge does not explain all of the features of AD. Twenty percent of affected individuals do not generate IgE responses to such ubiquitous proteins, and it is unclear why disease incidence changes during age and between different geographical regions. The risk of disease is clearly influenced by genetic susceptibility factors, some of which affect the immune response, e.g., polymorphisms of the Fc R1 and IL-4R genes (11-13). However, it is becoming increasingly clear from the genetic studies that skin-specific genes, determining variables s...

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“…Based on a polygenic inheritance [10], striking abnormalities in several components of the immune system have been described, such as elevated levels of total and specific IgE, blood and dermal eosinophilia as well as the infiltration of lesional skin with CD4 cells [7, 9, 11]. In acute lesions, CD4 cells are predominantly of the Th2 type, expressing and secreting IL-4, IL-5 and IL-13, whereas in chronic lesions IFN-γ-producing Th1 cells dominate the immune response [6].…”

Section: Introductionmentioning

confidence: 99%

Mouse Models of Atopic Eczema Critically Evaluated

Gutermuth¹,

Ollert

Ring³

et al. 2004

Int Arch Allergy Immunol

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Atopic eczema (AE) is a chronic relapsing inflammatory skin disorder with increasing prevalence in Western societies. Even though we have made considerable progress in understanding the cellular and molecular nature of cutaneous inflammation, the precise pathomechanisms of AE still remain elusive. Experimental animal models are indispensable tools to study the pathogenic mechanisms and to test novel therapeutic approaches in vivo. For AE a considerable number of mouse models have been proposed and have been used to study specific aspects of the disease, such as genetics, skin barrier defects, immune deviations, bacteria–host interactions or the role of cytokines or chemokines in the inflammatory process. While some models closely resemble human AE, others appear to reflect only specific aspects of the disease. Here we review the currently available mouse models of AE in light of the novel World Allergy Organization classification of eczematous skin diseases and evaluate them according to their clinical, histopathological and immunological findings. The pathogenetic analogies between mice and men will be discussed.

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Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis

Cited by 309 publications

References 44 publications

Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema

Much Atopy about the Skin: Genome-Wide Molecular Analysis of Atopic Eczema

Bacterial superantigen facilitates epithelial presentation of allergen to T helper 2 cells

Mouse Models of Atopic Eczema Critically Evaluated

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