Multi‐omics integration reveals a core network involved in host defence and hyperkeratinization in psoriasis. Issue 12 (19th December 2022)

• Record Type: Journal Article
• Authors: Deng, Jingwen; Leijten, Emmerik; Nordkamp, Michel Olde; Zheng, Guangjuan; Pouw, Juliëtte; Tao, Weiyang; Hartgring, Sarita; Balak, Deepak; Rijken, Rianne; Huang, Runyue; Radstake, Timothy; Lu, Chuanjian; Pandit, Aridaman
• Is Part Of: Clinical and translational medicine. Volume 12:Issue 12(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-19
• Subjects: gene network -- hyperkeratinization -- multi‐omics -- psoriasis; Clinical medicine -- Periodicals; Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 616.027
• DOI: 10.1002/ctm2.976
• Languages: English
• ISSNs: 2001-1326

Abstract

Abstract: Objectives: The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesional and non‐lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high‐throughput RNA‐sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling. Results: We found that lesional and non‐lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in neutrophil activation . By using co‐expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a 'core' set of genes that was functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria . Skin microbiome analysis revealed that the abundances of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the genes in core network . Conclusions: We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin. Abstract : There were dramatic differences between molecular profiles of lesional and non‐lesional skin. A core network of genes is strongly associated with local disease severity, and it involved in the regulations of inflammation and hyperkeratinization in psoriatic lesion. Microbial imbalance in skin environment is identified in psoriatic skin, and it is associated with the core network of genes.