ResTORing barrier function in the skin

Wang, Jocelyn; Kaplan, Mark H.; Yang, Kai

doi:10.1016/j.jaci.2019.10.007

Journal of Allergy and Clinical Immunology

2020

DOI: 10.1016/j.jaci.2019.10.007

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ResTORing barrier function in the skin

Jocelyn Wang

Mark H. Kaplan

Kai Yang

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2024

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Diminished γδ T Cells during Murine Allergic Skin Inflammation Is Mediated by IL-4 Signaling in Keratinocytes

Zhang,

Pajulas,

Niese

et al. 2024

The Journal of Immunology

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Atopic dermatitis results in diminished barrier function and altered production of antimicrobial peptides. Dendritic epidermal T cells (DETCs) play an important role in the wound repair and inflammation process. Our previous work identified an IL-4–dependent loss of DETCs in Stat6VT mice and in the MC903-induced skin inflammation mouse model. However, the mechanisms through which IL-4 mediates the loss of DETCs are unclear. In this study, we show that IL-4Rα germline knockout mice (Il4ra–/–) have increased DETCs, faster wound healing, and increased epidermal differentiation complex gene and fibronectin expression. The absence of IL-4Rα minimized the MC903-induced loss of DETCs, and reciprocal bone marrow chimera experiments in Il4ra–/– and wild-type mice demonstrated structural nonhematopoietic IL-4–responsive cell-mediated DETC homeostasis. Skin keratinocyte-derived IL-15 decreased dramatically in the MC903 model, while injection of IL-15 rescued DETC loss by promoting DETC proliferation and limiting apoptosis. Conditional deletion of IL-4Rα from keratinocytes using Il4rafl/fl K14-Cre mice showed an increase of DETCs, increased IL-15 production, and diminished skin inflammation following wounding. These results suggest that IL-4–dependent effects on DETCs in allergic skin inflammation are mediated by the IL-4Rα receptor of keratinocytes.

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Diminished γδ T Cells during Murine Allergic Skin Inflammation Is Mediated by IL-4 Signaling in Keratinocytes

Zhang,

Pajulas,

Niese

et al. 2024

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

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ResTORing barrier function in the skin

Cited by 1 publication

References 11 publications

Diminished γδ T Cells during Murine Allergic Skin Inflammation Is Mediated by IL-4 Signaling in Keratinocytes

Diminished γδ T Cells during Murine Allergic Skin Inflammation Is Mediated by IL-4 Signaling in Keratinocytes

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