52 95

Cited 0 times in

High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking property

Authors
 Brian Hyohyoung Lee  ;  Yoon Ji Bang  ;  Sung Ha Lim  ;  Seong-Jun Kang  ;  Sung Hee Kim  ;  Seunghee Kim-Schulze  ;  Chung-Gyu Park  ;  Hyun Je Kim  ;  Tae-Gyun Kim 
Citation
 EBIOMEDICINE, Vol.100 : 104985, 2024-02 
Journal Title
EBIOMEDICINE
Issue Date
2024-02
MeSH
Humans ; Psoriasis* / metabolism ; Receptors, CCR7 / metabolism ; Skin / metabolism ; T-Lymphocytes, Regulatory* ; Th17 Cells
Keywords
Chemokine receptors ; Mass cytometry ; Psoriasis ; Regulatory T cells ; Skin-trafficking
Abstract
Background

Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular properties of skin-homing psoriatic Tregs have not been well explored.

Methods

We designed an extensive 39 marker mass cytometry (CyTOF) panel to deeply profile the immune landscape of skin-homing Tregs from 31 people with psoriasis stratified by psoriasis area severity index score as mild (n = 15) to moderate-severe (n = 16) and 32 healthy controls. We further validated the findings with an in-vitro chemokine-mediated Treg migration assay, immunofluorescent imaging of normal and psoriatic lesional skin and analysed public single-cell RNA-sequencing datasets to expand upon our findings into the local tissue microenvironments.

Findings

We discovered an overall decrease in CLAhi Tregs and specifically, CLAhiCCR5+ Tregs in psoriasis. Functional markers CD39 and FoxP3 were elevated in psoriatic Tregs. However, CCR7 expression was significantly increased while CCR4 and CLA expression was reduced in psoriatic Tregs and CLAhi Tregs, which was associated with disease severity. Moreover, psoriatic Tregs revealed increased migratory capacity towards CCR7’s ligands, CCL19/CCL21. Interrogation of public single-cell RNA sequencing data confirmed reduced expression of skin-trafficking markers in lesional-skin Tregs compared to non-lesioned skin, further substantiated by immunofluorescent staining.

Interpretation

Psoriatic circulating Tregs showed an impaired skin-trafficking phenotype thus leading to insufficient suppression of ongoing inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis.
Files in This Item:
T202401318.pdf Download
DOI
10.1016/j.ebiom.2024.104985
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198681
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links