Details

Autor(en) / Beteiligte

• Liu, Jared
• Chang, Hsin-Wen
• Huang, Zhi-Ming
• Nakamura, Mio
• Sekhon, Sahil
• Ahn, Richard
• Munoz-Sandoval, Priscila
• Bhattarai, Shrishti
• Beck, Kristen M.
• Sanchez, Isabelle M.
• Yang, Eric
• Pauli, Mariela
• Arron, Sarah T.
• Fung-Leung, Wai-Ping
• Munoz, Ernesto
• Liu, Xuejun
• Bhutani, Tina
• North, Jeffrey
• Fourie, Anne M.
• Rosenblum, Michael D.
• Liao, Wilson

Titel

Single-cell RNA sequencing of psoriatic skin identifies pathogenic Tc17 cell subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer

Ist Teil von

• Journal of allergy and clinical immunology, 2021-06, Vol.147 (6), p.2370-2380

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Psoriasis is an inflammatory, IL-17–driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. We used single-cell RNA sequencing to compare CD8+ T-cell transcriptomic heterogeneity between psoriatic and healthy skin. We identified 11 transcriptionally diverse CD8+ T-cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed 2 Tc17 cell subsets that were metabolically divergent, were developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity and which achieved comparable or greater accuracy than IL17A in a support vector machine classifier of psoriasis and healthy transcriptomes. Despite high coinhibitory receptor expression in the Tc17 cell clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. Using high-resolution single-cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including 2 nonexhausted Tc17 cell subsets associated with disease severity.