@article{0f508d16caae4321aac08442987feae5,
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.",
keywords = "Aging, DETC, STAT3, Skint, epidermal-immune cell cross-talk, re-epithelialization, wound healing",
author = "Keyes, {Brice E.} and Siqi Liu and Amma Asare and Shruti Naik and John Levorse and Lisa Polak and Lu, {Catherine P.} and Maria Nikolova and Pasolli, {Hilda Amalia} and Elaine Fuchs",
note = "Funding Information: We thank Fuchs{\textquoteright} lab colleagues Irina Matos and E. Heller for help with microscopy; Shijing Luo and N. Oshimori for intellectual input and suggestions; M. Sribour and S. Hacker for technical assistance in the mouse facility; J. dela Cruz-Racelis for assistance in tissue sectioning and culture; E. Wong for genotyping; S. Larson for assistance in tissue explants. Rockefeller University{\textquoteright}s Comparative Bioscience Center (AAALAC accredited) provided care of mice in accordance with National Institutes of Health (NIH) guidelines and Flow Cytometry facility for FACS sorting. Weill Cornell Medical School Genomics Center conducted sequencing. E.F. is an Investigator of the Howard Hughes Medical Institute and a Senior Investigator of the Ellison Foundation for Aging Research. B.E.K. was funded by the NIH/NCI ( CA009673-36A1 ) and a Postdoctoral Fellowship from AFAR. S.L. is a Jane Coffin Childs Postdoctoral Fellow and a Women & Science Fellow. A.A. is the recipient of a Merck graduate fellowship and a Medical Scientist Training Program traineeship. S.N. is a Damon Runyon Postdoctoral Fellow. This study was supported by grants from the NIH ( R01-AR050452 ) and the Ellison Foundation (AG-SS-2965-12, E.F.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = nov,
day = "17",
doi = "10.1016/j.cell.2016.10.052",
language = "English (US)",
volume = "167",
pages = "1323--1338.e14",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}