Regulatory T Cells Control Vascular Adhesion Molecule Expression in Skin Under Inflammatory and Homeostatic Conditions

Objective

During skin inflammation, inhibition of adhesion of regulatory T cells (Tregs) to the dermal microvascular endothelium leads to exacerbation of inflammation, evidence that the dermal endothelium is a key target of the anti-inflammatory actions of Tregs. The aim of this study was to investigate the capacity of Tregs to control the expression of endothelial adhesion molecules in inflamed and resting skin.

Methods

Treg function was assessed in a two-challenge contact hypersensitivity (CHS) model, measuring dermal adhesion molecule expression via imaging of cleared skin. Treg depletion was achieved using Foxp3^DTR mice.

Results

CHS induced upregulation of E-selectin and ICAM-1 but not P-selectin and VCAM-1. Elimination of Tregs following CHS challenge resulted in exacerbated skin inflammation and enhanced expression of E-selectin, P-selectin and ICAM-1 in the dermal microvasculature. Multiphoton imaging revealed that at this phase of the response, Tregs were enriched near blood vessels and underwent dynamic migration adjacent to the microvasculature. Additionally, in skin that was not undergoing hapten challenge, absence of Tregs also resulted in upregulation of E-selectin and ICAM-1 in skin vessels.

Conclusions

These observations demonstrate that the microvascular endothelium is a target of the anti-inflammatory actions of Tregs in the skin, both during CHS and in steady-state skin.