title: Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin.
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.
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Brice E
authors.initials: BE
authors.lastname: Keyes
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Amma
authors.initials: A
authors.lastname: Asare
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: John
authors.initials: J
authors.lastname: Levorse
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Polak
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Lu
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolova
authors.affiliation: The Rockefeller University, New York, NY 10065, USA.
authors.forename: Hilda Amalia
authors.initials: HA
authors.lastname: Pasolli
authors.affiliation: The Rockefeller University, New York, NY 10065, USA. Electronic address: fuchslb@rockefeller.edu.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015850:Interleukin-6 / Q000008:administration & dosage; D015603:Keratinocytes / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology*; D051379:Mice; D015398:Signal Transduction; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena; D014945:Wound Healing / Q000187:drug effects
chemical_list: D015850:Interleukin-6
keywords: Aging; DETC; STAT3; Skint; epidermal-immune cell cross-talk; re-epithelialization; wound healing