Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 Nov 19

PMID 27863246

Citations 133

Authors

Brice E Keyes

Siqi Liu

Amma Asare

Shruti Naik

John Levorse

Lisa Polak

Catherine P Lu

Maria Nikolova

Hilda Amalia Pasolli

Elaine Fuchs

Affiliations

Soon will be listed here.

Abstract

Aged skin heals wounds poorly, increasing susceptibility to infections. Restoring homeostasis after wounding requires the coordinated actions of epidermal and immune cells. Here we find that both intrinsic defects and communication with immune cells are impaired in aged keratinocytes, diminishing their efficiency in restoring the skin barrier after wounding. At the wound-edge, aged keratinocytes display reduced proliferation and migration. They also exhibit a dampened ability to transcriptionally activate epithelial-immune crosstalk regulators, including a failure to properly activate/maintain dendritic epithelial T cells (DETCs), which promote re-epithelialization following injury. Probing mechanism, we find that aged keratinocytes near the wound edge don't efficiently upregulate Skints or activate STAT3. Notably, when epidermal Stat3, Skints, or DETCs are silenced in young skin, re-epithelialization following wounding is perturbed. These findings underscore epithelial-immune crosstalk perturbations in general, and Skints in particular, as critical mediators in the age-related decline in wound-repair.

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