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

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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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Acknowledgements

This work was supported by the Dermatology Foundation (Physician-Scientist CDA) to MJT, The Department of Veterans Affairs VA CDA2 (IK2 CX001019) to MJT and VA Merit (510BX000853) to JBT, the Ralph W. and Grace M. Showalter Research Trust to MJT and NIH grants to MHK (R01 AI095282), DFS (AG048946 and ES020866), and JBT (HL062996, AG048946, and ES020866). MRO and AK were supported by T32 AR062495.

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Correspondence to Matthew J. Turner.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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DaSilva-Arnold, S.C., Thyagarajan, A., Seymour, L.J. et al. Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis. Arch Dermatol Res 310, 197–207 (2018). https://doi.org/10.1007/s00403-018-1807-y

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  • DOI: https://doi.org/10.1007/s00403-018-1807-y

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