Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis

Sonia C. DaSilva-Arnold, Anita Thyagarajan, Leroy J. Seymour, Qiaofang Yi, Joshua R. Bradish, Mohammed Al-Hassani, Hongming Zhou, Nikolajs J. Perdue, Val Nemeth, Aleksandar Krbanjevic, Ana P.M. Serezani, Matthew R. Olson, Dan Spandau, Jeffrey Travers, Mark Kaplan, Matthew J. Turner

Research output: Contribution to journalArticle

Abstract

The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalArchives of Dermatological Research
DOIs
StateAccepted/In press - Jan 24 2018

Fingerprint

Atopic Dermatitis
Keratinocytes
STAT6 Transcription Factor
Keratin-5
Skin
Interleukin-33
Fluorescent Antibody Technique
Chronic Disease
Cytokines
Inflammation
T-Lymphocytes

Keywords

  • Atopic dermatitis
  • Eczema
  • Interleukin 33 (IL-33)
  • Keratinocytes
  • Stat6VT transgenic mouse

ASJC Scopus subject areas

  • Dermatology

Cite this

DaSilva-Arnold, S. C., Thyagarajan, A., Seymour, L. J., Yi, Q., Bradish, J. R., Al-Hassani, M., ... Turner, M. J. (Accepted/In press). Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis. Archives of Dermatological Research, 1-11. https://doi.org/10.1007/s00403-018-1807-y

Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis. / DaSilva-Arnold, Sonia C.; Thyagarajan, Anita; Seymour, Leroy J.; Yi, Qiaofang; Bradish, Joshua R.; Al-Hassani, Mohammed; Zhou, Hongming; Perdue, Nikolajs J.; Nemeth, Val; Krbanjevic, Aleksandar; Serezani, Ana P.M.; Olson, Matthew R.; Spandau, Dan; Travers, Jeffrey; Kaplan, Mark; Turner, Matthew J.

In: Archives of Dermatological Research, 24.01.2018, p. 1-11.

Research output: Contribution to journalArticle

DaSilva-Arnold, SC, Thyagarajan, A, Seymour, LJ, Yi, Q, Bradish, JR, Al-Hassani, M, Zhou, H, Perdue, NJ, Nemeth, V, Krbanjevic, A, Serezani, APM, Olson, MR, Spandau, D, Travers, J, Kaplan, M & Turner, MJ 2018, 'Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis', Archives of Dermatological Research, pp. 1-11. https://doi.org/10.1007/s00403-018-1807-y
DaSilva-Arnold, Sonia C. ; Thyagarajan, Anita ; Seymour, Leroy J. ; Yi, Qiaofang ; Bradish, Joshua R. ; Al-Hassani, Mohammed ; Zhou, Hongming ; Perdue, Nikolajs J. ; Nemeth, Val ; Krbanjevic, Aleksandar ; Serezani, Ana P.M. ; Olson, Matthew R. ; Spandau, Dan ; Travers, Jeffrey ; Kaplan, Mark ; Turner, Matthew J. / Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis. In: Archives of Dermatological Research. 2018 ; pp. 1-11.
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abstract = "The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system.",
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AU - DaSilva-Arnold, Sonia C.

AU - Thyagarajan, Anita

AU - Seymour, Leroy J.

AU - Yi, Qiaofang

AU - Bradish, Joshua R.

AU - Al-Hassani, Mohammed

AU - Zhou, Hongming

AU - Perdue, Nikolajs J.

AU - Nemeth, Val

AU - Krbanjevic, Aleksandar

AU - Serezani, Ana P.M.

AU - Olson, Matthew R.

AU - Spandau, Dan

AU - Travers, Jeffrey

AU - Kaplan, Mark

AU - Turner, Matthew J.

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N2 - The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system.

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