Pathogenesis of Atopic Dermatitis: Current Paradigm

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal r...

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Vydáno v:	Iranian journal of immunology Ročník 16; číslo 2; s. 97 - 107
Hlavní autoři:	Furue, Masutaka, Ulzii, Dugarmaa, Vu, Yen Hai, Tsuji, Gaku, Kido-Nakahara, Makiko, Nakahara, Takeshi
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Iran Shiraz University of Medical Sciences 01.06.2019 Shiraz Institute for Cancer Research
Témata:	Allergens Antibodies Antibodies, Monoclonal, Humanized Antibodies, Monoclonal, Humanized - therapeutic use Atopic dermatitis Biology (General) CCL17 protein CCL22 protein Chemokines Cytokines Cytokines - metabolism Dendritic cells Dermatitis Dermatitis, Atopic Dermatitis, Atopic - drug therapy Dermatitis, Atopic - immunology Dermatology Drug development Eczema Epidermis Epidermis - pathology Filaggrin Filaggrin Proteins Gene expression Histamine Humans il-13 il-31 il-4 Immune deviation Inflammation Interleukin 13 Interleukin 4 Intermediate Filament Proteins Intermediate Filament Proteins - metabolism Keratinocytes Keratinocytes - physiology Lymphocytes T Monoclonal antibodies ox40 OX40 Ligand OX40 Ligand - metabolism Ox40L protein Pathogenesis Patients Pediatrics Pruritus QH301-705.5 Receptors, Interleukin-4 Receptors, Interleukin-4 - immunology Receptors, OX40 Receptors, OX40 - metabolism Sensory neurons Signal Transduction Skin diseases Th2 Cells Th2 Cells - immunology Thymic stromal lymphopoietin Thymus Tumor necrosis factor
ISSN:	1735-367X, 1735-1383, 1735-367X
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Popis
Shrnutí:	Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction and chronic pruritus. In this review, recent advances in the pathogenesis of AD are summarized. Clinical efficacy of the anti-IL-4 receptor antibody dupilumab implies that type 2 cytokines IL-4 and IL-13 have pivotal roles in atopic inflammation. The expression of IL-4 and IL-13 as well as type 2 chemokines such as CCL17, CCL22 and CCL26 is increased in the lesional skin of AD. In addition, IL-4 and IL-13 down-regulate the expression of filaggrin in keratinocytes and exacerbate epidermal barrier dysfunction. Keratinocytes in barrier-disrupted epidermis produce large amounts of thymic stromal lymphopoietin, IL-25 and IL-33, conducing to type 2 immune deviation via OX40L/OX40 signaling. IL-31, produced by type 2 T cells, is a cardinal pruritogenic cytokine. IL-4 and IL-13 also amplify the IL-31-mediated sensory nerve signal. These molecules are particularly important targets for future drug development for AD.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	1735-367X 1735-1383 1735-367X
DOI:	10.22034/iji.2019.80253