The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation

Y. Mitamura, S. Nunomura, Y. Nanri, M. Ogawa, T. Yoshihara, M. Masuoka, G. Tsuji, T. Nakahara, A. Hashimoto-Hachiya, S. J. Conway, M. Furue, K. Izuhara

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1881-1891
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume73
Issue number9
DOIs
StatePublished - Sep 2018

Keywords

  • IL-13
  • IL-24
  • atopic dermatitis
  • barrier dysfunction
  • periostin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Mitamura, Y., Nunomura, S., Nanri, Y., Ogawa, M., Yoshihara, T., Masuoka, M., Tsuji, G., Nakahara, T., Hashimoto-Hachiya, A., Conway, S. J., Furue, M., & Izuhara, K. (2018). The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation. Allergy: European Journal of Allergy and Clinical Immunology, 73(9), 1881-1891. https://doi.org/10.1111/all.13437