한빛사논문
- 조회294
Yale Liu 1 2 3 †, Hao Wang 4 †, Mark Taylor 2, Christopher Cook 2 3, Alejandra Martínez-Berdeja 2, Jeffrey P North 2, Paymann Harirchian 2 3, Ashley A Hailer 2 3, Zijun Zhao 5, Ruby Ghadially 2 3, Roberto R Ricardo-Gonzalez 2 6, Roy C Grekin 2, Theodora M Mauro 2 3, Esther Kim 7, Jaehyuk Choi 8, Elizabeth Purdom 4, Raymond J Cho 2 *, Jeffrey B Cheng 2 3 *
1Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, ShaanXi 710004, P. R. China.
2Department of Dermatology, University of California, San Francisco, San Francisco, CA 94107, USA.
3Dermatology, Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
4Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA.
5Santa Clara Valley Medical Center, Santa Clara, CA 95128, USA.
6Department of Immunology and Microbiology, University of California, San Francisco, San Francisco, CA 94143, USA.
7Department of Plastic Surgery, University of California, San Francisco, San Francisco, CA 94107, USA.
8Department of Dermatology, Northwestern School of Medicine, Chicago, IL 60611, USA.
†These authors contributed equally
*Corresponding authors: correspondence to Raymond J Cho or Jeffrey B Cheng
Abstract
Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45+ immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the Treg and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8+ cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (TH2)/TH17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq-derived data in the context of our TH2/TH17 transcriptional framework.
논문정보
- Research article
- 2022년 04월 (BRIC 등록일 2024-01-31)
- 국외 연구진
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