김현제 (서울대학교) | 한빛사논문 > 한빛사

한빛사논문

조회723

서울대학교

CV File 391 kb

EBioMedicine, Feb 01 2024, 100 S2352-3964(24)00020-3 | https://doi.org/10.1016/j.ebiom.2024.104985 High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-trafficking property

Brian Hyohyoung Lee ^a,b,l, Yoon Ji Bang ^a,l, Sung Ha Lim ^c,l, Seong-Jun Kang ^a,d, Sung Hee Kim ^e, Seunghee Kim-Schulze ^b, Chung-Gyu Park ^a,d,f,g,h,i, Hyun Je Kim ^a,d,f,g,i,j, Tae-Gyun Kim ^e,k

^aDepartment of Biomedical Sciences, Seoul National University Graduate School, Seoul, South Korea

^bHuman Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA

^cDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju, South Korea

^dCancer Research Institute, Seoul National University, Seoul, South Korea

^eDepartment of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea

^fDepartment of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea

^gInstitute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, South Korea

^hTransplantation Research Institute, Seoul National University Medical Research Center, Seoul, South Korea

ⁱSeoul National University Hospital, Seoul, South Korea

^jGenome Medicine Institute, Seoul National University Medical Research Center, Seoul, South Korea

^kInstitute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea

^lThese authors contributed equally to this work.

Corresponding authors: Chung-Gyu Park, Hyun Je Kim, Tae-Gyun Kim

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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-05)
연구진국내(교신)+국외 연구진
분야 의약학 > 응용의학

댓글 작성 로그인

CV 열람하기

연락처 보기