Journal: iScience

Article Title: A stress-responsive neurovascular axis shapes skin immune accessibility

doi: 10.1016/j.isci.2026.115122

Figure Lengend Snippet: Norepinephrine increases vascular permeability and exacerbates skin diseases via α2B-adrenergic receptor signaling (A) Plasma NE levels in control, stressed, and UV-irradiated mice measured by ELISA ( n = 5–6 mice per condition). (B) Guanethidine (Gua) injection inhibits NE release from the sympathetic nerve. Right, quantification of Evans blue dye extravasation in the skin of control and stressed mice pretreated with PBS or Gua ( n = 5–6 mice per condition). (C) TRITC-dextran extravasation in mouse skin after intravenous PBS or NE. Right, fluorescence intensity quantification of TRITC-dextran ( n = 4 mice per condition). (D) The adrenergic receptor (AR) system is categorized into three subtypes: α1, α2, and β; yohimbine is a classical α2-AR antagonist. (E) Representative images and quantification of Evans blue extravasation in the skin of control and stressed mice pretreated with PBS or yohimbine ( n = 3–8 mice per condition). (F) The three α2-AR subtypes (α2A, α2B, α2C) and their selective antagonists: BRL-44408 (α2A), ARC-239 (α2B), JP-1302 (α2C). (G) Quantification of Evans blue extravasation in the skin of control mice and stressed mice pretreated with PBS or three α2-AR subtype-specific antagonists. ( n = 6–7 mice per condition). (H) Representative images and quantification of Evans blue extravasation in the skin of WT and Adra2b knockout (KO) mice under stressed or non-stressed conditions ( n = 4–8 mice per condition). (I) Quantification of TRITC-dextran extravasation in the skin of WT and Adra2b KO mice after intravenous injection of NE ( n = 4 mice per condition). (J) Schematic of live imaging of TRITC-dextran extravasation in WT and Adra2b KO mice after NE injection. (K) In vivo imaging of dermal vascular leakage in WT and Adra2b KO mice after NE and TRITC-dextran injection (imaged at 0/5/10 min). (L) Psoriasis induction by IMQ in stressed or non-stressed WT and Adra2b KO mice. (M) Representative histological sections of IMQ-treated dorsal skin of WT and Adra2b KO mice under stressed or non-stressed conditions. (N) Quantification of epidermal thickness in IMQ-induced skin of WT and Adra2b KO mice with or without stress ( n = 7–10 mice per condition). (O) AD induction by MC903 in WT and Adra2b KO mice with or without UV exposure. (P) Representative histological sections of dorsal skin from WT or Adra2b KO mice after MC903-induced AD, with or without UV irradiation. (Q) Quantification of epidermal thickness in AD skin lesions of WT and Adra2b KO mice with or without UV irradiation ( n = 5 mice per condition). Scale bars, 5 mm in insets in (E) and (H); 100 μm in insets in (M) and (P); 50 μm elsewhere. Data are mean ± SEM. Data were analyzed using an unpaired two-tailed Student’s t test. ∗ : p < 0.05, ∗∗ : p < 0.01, ∗∗∗ : p < 0.001, and ∗∗∗∗ : p < 0.0001; n.s.: not significant.

Article Snippet: ARC 239 dihydrochloride , MedChemExpress , Cat# HY-12709A.

Techniques: Permeability, Clinical Proteomics, Control, Irradiation, Enzyme-linked Immunosorbent Assay, Injection, Fluorescence, Knock-Out, Imaging, In Vivo Imaging, Two Tailed Test