Dendritic epidermal T cells regulate skin antimicrobial barrier function
Amanda S. MacLeod, … , Deborah A. Witherden, Wendy L. Havran
Amanda S. MacLeod, … , Deborah A. Witherden, Wendy L. Havran
Published September 24, 2013
Citation Information: J Clin Invest. 2013;123(10):4364-4374. https://doi.org/10.1172/JCI70064.
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Research Article Immunology

Dendritic epidermal T cells regulate skin antimicrobial barrier function

Abstract

The epidermis, the outer layer of the skin, forms a physical and antimicrobial shield to protect the body from environmental threats. Skin injury severely compromises the epidermal barrier and requires immediate repair. Dendritic epidermal T cells (DETC) reside in the murine epidermis where they sense skin injury and serve as regulators and orchestrators of immune responses. Here, we determined that TCR stimulation and skin injury induces IL-17A production by a subset of DETC. This subset of IL-17A–producing DETC was distinct from IFN-γ producers, despite similar surface marker profiles. Functionally, blocking IL-17A or genetic deletion of IL-17A resulted in delayed wound closure in animals. Skin organ cultures from Tcrd–/–, which lack DETC, and Il17a–/– mice both exhibited wound-healing defects. Wound healing was fully restored by the addition of WT DETC, but only partially restored by IL-17A–deficient DETC, demonstrating the importance of IL-17A to wound healing. Following skin injury, DETC-derived IL-17A induced expression of multiple host-defense molecules in epidermal keratinocytes to promote healing. Together, these data provide a mechanistic link between IL-17A production by DETC, host-defense, and wound-healing responses in the skin. These findings establish a critical and unique role of IL-17A–producing DETC in epidermal barrier function and wound healing.

Authors

Amanda S. MacLeod, Saskia Hemmers, Olivia Garijo, Marianne Chabod, Kerri Mowen, Deborah A. Witherden, Wendy L. Havran

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Figure 4

IL-17A– and IFN-γ–producing DETC subsets maintain their CD27–45RB+ phenotype.

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IL-17A– and IFN-γ–producing DETC subsets maintain their CD27–45RB+ pheno...
(A) Phenotypic characterization of freshly isolated WT and Il17a–/– DETC. Cells are gated on Vγ3+Thy1.2+ and CD45RB, CD27, NK1.1, CD62L, CD122, IL-7R, and CD69 expression (solid lines), and their appropriate IgG controls (gray) were measured by flow cytometry. (B) Distinct DETC subsets produce IL-17A and IFN-γ. Intracellular staining on DETC short-term cell lines stimulated with anti-CD3ε (10 μg/ml) for IL-17A and IFN-γ production. Cells are gated on Vγ3+Thy1.2+. (C) IL-17A– and IFN-γ–producing DETC are CD27–CD45RB+. Fresh epidermal cell suspensions were stimulated with anti-CD3ε (10 μg/ml), and expression of CD27, CD45RB, and intracellular IL-17A and IFN-γ were measured by flow cytometry. Cells are gated on IL-17A+Vγ3+Thy1.2+ and IFN-γ+Vγ3+Thy1.2+, respectively.