Fibroblast inflammatory priming determines regenerative versus fibrotic skin repair in reindeer.
fetal human fibroblast
fibroblast
immune modulation
inflammation
inflammatory priming
myeloid cell maturation
reindeer
scar
skin regeneration
stromal-immune crosstalk
wound healing
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
08 Dec 2022
08 Dec 2022
Historique:
received:
21
09
2021
revised:
24
08
2022
accepted:
02
11
2022
entrez:
9
12
2022
pubmed:
10
12
2022
medline:
15
12
2022
Statut:
ppublish
Résumé
Adult mammalian skin wounds heal by forming fibrotic scars. We report that full-thickness injuries of reindeer antler skin (velvet) regenerate, whereas back skin forms fibrotic scar. Single-cell multi-omics reveal that uninjured velvet fibroblasts resemble human fetal fibroblasts, whereas back skin fibroblasts express inflammatory mediators mimicking pro-fibrotic adult human and rodent fibroblasts. Consequently, injury elicits site-specific immune responses: back skin fibroblasts amplify myeloid infiltration and maturation during repair, whereas velvet fibroblasts adopt an immunosuppressive phenotype that restricts leukocyte recruitment and hastens immune resolution. Ectopic transplantation of velvet to scar-forming back skin is initially regenerative, but progressively transitions to a fibrotic phenotype akin to the scarless fetal-to-scar-forming transition reported in humans. Skin regeneration is diminished by intensifying, or enhanced by neutralizing, these pathologic fibroblast-immune interactions. Reindeer represent a powerful comparative model for interrogating divergent wound healing outcomes, and our results nominate decoupling of fibroblast-immune interactions as a promising approach to mitigate scar.
Identifiants
pubmed: 36493752
pii: S0092-8674(22)01414-3
doi: 10.1016/j.cell.2022.11.004
pmc: PMC9888357
mid: NIHMS1849249
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4717-4736.e25Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR070313
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001998
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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