CD80 on skin stem cells promotes local expansion of regulatory T cells upon injury to orchestrate repair within an inflammatory environment Journal Article


Authors: Luan, J.; Truong, C.; Vuchkovska, A.; Guo, W.; Good, J.; Liu, B.; Gang, A.; Infarinato, N.; Stewart, K.; Polak, L.; Pasolli, H. A.; Andretta, E.; Rudensky, A. Y.; Fuchs, E.; Miao, Y.
Article Title: CD80 on skin stem cells promotes local expansion of regulatory T cells upon injury to orchestrate repair within an inflammatory environment
Abstract: Following tissue damage, epithelial stem cells (SCs) are mobilized to enter the wound, where they confront harsh inflammatory environments that can impede their ability to repair the injury. Here, we investigated the mechanisms that protect skin SCs within this inflammatory environment. Characterization of gene expression profiles of hair follicle SCs (HFSCs) that migrated into the wound site revealed activation of an immune-modulatory program, including expression of CD80, major histocompatibility complex class II (MHCII), and CXC motif chemokine ligand 5 (CXCL5). Deletion of CD80 in HFSCs impaired re-epithelialization, reduced accumulation of peripherally generated Treg (pTreg) cells, and increased infiltration of neutrophils in wounded skin. Importantly, similar wound healing defects were also observed in mice lacking pTreg cells. Our findings suggest that upon skin injury, HFSCs establish a temporary protective network by promoting local expansion of Treg cells, thereby enabling re-epithelialization while still kindling inflammation outside this niche until the barrier is restored. © 2024 The Authors
Keywords: controlled study; nonhuman; flow cytometry; transcription factor foxp3; antigen expression; cell proliferation; animal cell; mouse; animal; electron microscopy; metabolism; animals; mice; mice, knockout; animal tissue; gene expression profiling; animal experiment; animal model; inflammation; cell motion; in vitro study; pathology; mice, inbred c57bl; c57bl mouse; stem cell; skin; wound healing; regulatory t lymphocyte; immunology; t-lymphocytes, regulatory; cell isolation; lentivirus; cell migration; cell movement; epithelium cell; stem cells; neutrophils; bone marrow cell; c57bl 6 mouse; epithelization; major histocompatibility complex; wound healing impairment; fluorescence activated cell sorting; neutrophil chemotaxis; knockout mouse; b7 antigen; rna extraction; coculture; skin injury; rna isolation; hair follicle; hair follicle stem cell; wound repair; epithelial derived neutrophil activating factor 78; high throughput sequencing; cd80; article; immunofluorescence assay; gene set enrichment analysis; hek293-ft cell line; interventional ultrasonography; single cell rna seq; treg cell; b7-1 antigen; re-epithelialization
Journal Title: Immunity
Volume: 57
Issue: 5
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2024-05-14
Start Page: 1071
End Page: 1086.e7
Language: English
DOI: 10.1016/j.immuni.2024.04.003
PUBMED: 38677291
PROVIDER: scopus
PMCID: PMC11265648
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Alexander Rudensky
    156 Rudensky