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, Simon Conway, M. Furue, K. Izuhara

Research output: Contribution to journalArticle

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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 1 2018

Fingerprint

Interleukin-13
Inflammation
Skin
Atopic Dermatitis
Down-Regulation
Mites
Keratinocytes
Epidermis
Interleukin-4
Oligonucleotide Array Sequence Analysis
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation. / Mitamura, Y.; Nunomura, S.; Nanri, Y.; Ogawa, M.; Yoshihara, T.; Masuoka, M.; Tsuji, G.; Nakahara, T.; Hashimoto-Hachiya, A.; Conway, Simon; Furue, M.; Izuhara, K.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 73, No. 9, 01.09.2018, p. 1881-1891.

Research output: Contribution to journalArticle

Mitamura, Y, Nunomura, S, Nanri, Y, Ogawa, M, Yoshihara, T, Masuoka, M, Tsuji, G, Nakahara, T, Hashimoto-Hachiya, A, Conway, S, 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, vol. 73, no. 9, pp. 1881-1891. https://doi.org/10.1111/all.13437
Mitamura, Y. ; Nunomura, S. ; Nanri, Y. ; Ogawa, M. ; Yoshihara, T. ; Masuoka, M. ; Tsuji, G. ; Nakahara, T. ; Hashimoto-Hachiya, A. ; Conway, Simon ; Furue, M. ; Izuhara, K. / The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation. In: Allergy: European Journal of Allergy and Clinical Immunology. 2018 ; Vol. 73, No. 9. pp. 1881-1891.
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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.",
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AU - Mitamura, Y.

AU - Nunomura, S.

AU - Nanri, Y.

AU - Ogawa, M.

AU - Yoshihara, T.

AU - Masuoka, M.

AU - Tsuji, G.

AU - Nakahara, T.

AU - Hashimoto-Hachiya, A.

AU - Conway, Simon

AU - Furue, M.

AU - Izuhara, K.

PY - 2018/9/1

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N2 - 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.

AB - 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.

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