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

Abstract

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 IL17A and IL22 . 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 IL17A, IL22 , and IL23A 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 IL17A and IL22 . 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.

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

“…Publicly available datasets were analyzed by unsupervised clustering using t-Distributed Stochastic Neighbor Embedding (t-SNE) dimensionality reduction. Although the analyses of Le et al support the idea of a close relationship between IL-17A and IL-23, their results are rather indicative for separate IL-17A-and IL-22-secreting T cells instead of a dual secreting phenotype [63].…”

Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases

“…Previous findings suggest that IL-22 in the psoriatic epidermis is produced by IL22 + IL-17 + Th17 cells. Recent studies show that there is no significant correlation between the expression of IL-17A and IL-22 in psoriasis, which does not support the existence of double-secreted IL-17A/IL-22 Th17 cells ( 114 ).…”

New Frontiers in Psoriatic Disease Research, Part I: Genetics, Environmental Triggers, Immunology, Pathophysiology, and Precision Medicine

“…However, in the near future, clinicians will be able to utilize more sophisticated approaches that integrate clinical phenotypic data with predictive or diagnostic classifiers constructed from omic datasets, such as for the transcriptome (Le et al, 2019;Li et al, 2014;Merleev et al, 2018;Tsoi et al, 2019), genome (Supplementary Table S1), microbiome (Supplementary Table S1), lipidome (Sorokin et al, 2018;, glycome (Li et al, 2019;Maverakis et al, 2015;Park et al, 2018), proteome (Broome et al, 2003;Carlén et al, 2005), and metabolome . Recent technologies such as single-cell RNA sequencing have begun to identify novel cell subsets in the skin and synovium (Cheng et al, 2018;Croft et al, 2019;Liu et al, 2020a;Orange et al, 2018;Stephenson et al, 2018).…”