TAR is not related to the skin barrier status and is driven by local signal(s) in situ.

<p><b>(A)</b> Tissue sections of WT mice ear skin at baseline (no Tx) and 12 h after a single topical application of acetone, immunostained for Ly6g and K14 (nuclei stained with DAPI). Scale bars: 50 μm. epi, epidermis; derm, dermis; hf, hair follicle. Dashed lines depict the dermo-epidermal interface. <b>(B)</b> Trans-epidermal water loss measurements (TEWL) of mouse ears treated with a single dose of acetone or TPA. <i>n</i> = 6. Two-way ANOVA. <b>(C)</b> Strategy to test whether TAR is mediated by local or systemic signals. Dual TPA treatment was applied to either the same ear (“local”) or contra-lateral ears (“distant”), 24 h apart. Clipart is open source <a href="https://openclipart.org/detail/17622/simple-cartoon-mouse-1" target="_blank">https://openclipart.org/detail/17622/simple-cartoon-mouse-1</a>; Creative Commons CC0 1.0 Universal License (<a href="https://creativecommons.org/publicdomain/zero/1.0/" target="_blank">https://creativecommons.org/publicdomain/zero/1.0/</a>). <b>(D)</b> Tissue sections from (C) were immunostained for Ly6g, K14, and nuclei (DAPI). Scale bars: 50 μm. <b>(E)</b> Quantitation of neutrophil fluorescence signal (surface area measurements) of data in C, <i>n</i> = 3 mice. Data reported as mean ± SEM. One-way ANOVA. The source data used to derive the numerical values reported here can be found in <b><a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3002779#pbio.3002779.s016" target="_blank">S1 Data</a></b>.</p> <p>(PDF)</p>