Jared Liu, PhD, Hsin-Wen Chang, PhD, Zhi-Ming Huang, PhD, Mio Nakamura, MD, Sahil Sekhon, MD, Richard Ahn, PhD, Priscila Munoz-Sandoval, BA, ShrishtiBhattarai, MS, Kristen M. Beck, MD, Isabelle M. Sanchez, MD, Eric Yang, MD, Mariela Pauli, MS, Sarah T. Arron, MD, PhD, Wai-Ping Fung-Leung, PhD, ErnestoMunoz, PhD, Xuejun Liu, PhD, Tina Bhutani, MD, MAS, Jeffrey North, MD, Anne M.Fourie, PhD, Michael D. Rosenblum, MD, PhD, Wilson Liao, MD
Background: Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. Objective: Our study focused on comprehensively characterizing the phenotypic variation of CD8+ T cells in psoriatic lesions. Methods: We used single-cell RNA-seq to compare CD8+ T cell transcriptomic heterogeneity between psoriatic and healthy skin. Results: We identified 11 transcriptionally diverse CD8+ T cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed two Tc17 subsets that were metabolically divergent, 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 co-inhibitory receptor expression in the Tc17 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. Conclusion: Using high resolution single cell profiling in tissue, we have uncovered the diverse landscape of CD8+ T cells in psoriatic and healthy skin, including two non-exhausted Tc17 subsets associated with disease severity.