The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation.
Allergy
; 73(9): 1881-1891, 2018 Sep.
Article
em En
| MEDLINE
| ID: mdl-29528494
ABSTRACT
BACKGROUND:
Barrier dysfunction is an important feature of atopic dermatitis (AD) in which IL-4 and IL-13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL-4 or IL-13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL-13 signal.METHODS:
We systematically identified periostin-dependent expression profile using DNA microarrays. We then investigated whether IL-24 downregulates filaggrin expression downstream of the IL-13 signals and whether IL-13-induced IL-24 expression and IL-24-induced downregulation of filaggrin expression are dependent on the JAK/STAT pathway. To build on the significance of in vitro findings, we investigated expression of IL-24 and activation of STAT3 in mite-treated mice and in AD patients.RESULTS:
We identified IL-24 as an IL-13-induced molecule in a periostin-dependent manner. Keratinocytes are the main IL-24-producing tissue-resident cells stimulated by IL-13 in a periostin-dependent manner via STAT6. IL-24 significantly downregulated filaggrin expression via STAT3, contributing to barrier dysfunction downstream of the IL-13/periostin pathway. Wild-type mite-treated mice showed significantly enhanced expression of IL-24 and activation of STAT3 in the epidermis, which disappeared in both STAT6-deficient and periostin-deficient mice, suggesting that these events are downstream of both STAT6 and periostin. Moreover, IL-24 expression was enhanced in the epidermis of skin tissues taken from AD patients.CONCLUSIONS:
The IL-13/periostin pathway induces IL-24 production in keratinocytes, playing an important role in barrier dysfunction in AD.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Moléculas de Adesão Celular
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Interleucinas
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Interleucina-13
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Dermatite Atópica
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Epiderme
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Animals
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article