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The IL ‐13/periostin/ IL ‐24 pathway causes epidermal barrier dysfunction in allergic skin inflammation
Author(s) -
Mitamura Y.,
Nunomura S.,
Nanri Y.,
Ogawa M.,
Yoshihara T.,
Masuoka M.,
Tsuji G.,
Nakahara T.,
HashimotoHachiya A.,
Conway S. J.,
Furue M.,
Izuhara K.
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13437
Subject(s) - periostin , filaggrin , matricellular protein , interleukin 13 , downregulation and upregulation , allergic inflammation , stat3 , inflammation , immunology , signal transduction , interleukin , biology , microbiology and biotechnology , atopic dermatitis , cytokine , extracellular matrix , biochemistry , gene
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 STAT 3 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 STAT 6. IL ‐24 significantly downregulated filaggrin expression via STAT 3, 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 STAT 3 in the epidermis, which disappeared in both STAT 6‐deficient and periostin‐deficient mice, suggesting that these events are downstream of both STAT 6 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 .