2D Visualization of the Psoriasis Transcriptome Fails to Support the Existence of Dual-Secreting IL-17A/IL-22 Th17 T Cells

• Published in: Frontiers in immunology 2019-04, Vol.10, p.589-589
• Main Authors: Le, Stephanie T, Merleev, Alexander A, Luxardi, Guillaume, Shimoda, Michiko, Adamopoulos, Iannis E, Tsoi, Lam C, Wang, Jenny Z, Alexanian, Claire, Raychaudhuri, Siba P, Hwang, Samuel T, Gudjonsson, Johann, Marusina, Alina I, Maverakis, Emanual
• Format: Article
• Language: English
• Subjects: Biomarkers; Computational Biology - methods; Cytokines - biosynthesis; Disease Susceptibility; Gene Expression Profiling; Gene Expression Regulation; Humans; IL17; IL22; Immunology; Inflammation Mediators - metabolism; Interleukin-17 - biosynthesis; Interleukin-22; Interleukins - biosynthesis; machine learning; Molecular Imaging; neutrophil; psoriasis; Psoriasis - etiology; Psoriasis - metabolism; Psoriasis - pathology; RNA-seq; Th17 Cells - immunology; Th17 Cells - metabolism; Transcriptome
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.00589

The present paradigm of psoriasis pathogenesis revolves around the IL-23/IL-17A axis. Dual-secreting Th17 T cells presumably are the predominant sources of the psoriasis phenotype-driving cytokines, IL-17A and IL-22. We thus conducted a meta-analysis of independently acquired RNA-seq psoriasis datasets to explore the relationship between the expression of and . This analysis failed to support the existence of dual secreting IL-17A/IL-22 Th17 cells as a major source of these cytokines. However, variable relationships amongst the expression of psoriasis susceptibility genes and of , and were identified. Additionally, to shed light on gene expression relationships in psoriasis, we applied a machine learning nonlinear dimensionality reduction strategy (t-SNE) to display the entire psoriasis transcriptome as a 2-dimensonal image. This analysis revealed a variety of gene clusters, relevant to psoriasis pathophysiology but failed to support a relationship between and . These results support existing theories on alternative sources of IL-17A and IL-22 in psoriasis such as a Th22 cells and non-T cell populations.