Balak, D. | bioRxiv Science

bioRxiv2024

Single-cell Landscape of Immune Cells in Blood and Skin in Psoriasis

BackgroundPsoriasis is a systemic inflammatory disease for which there is currently no cure, in part due to an incomplete understanding of its pathophysiology. MethodsTo better understand the immune response in psoriasis, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) and on lesional and non-lesional skin samples from a cohort of 11 psoriasis patients and 8 healthy controls. Additionally, we conducted flow cytometry on PBMCs from a separate cohort of 13 psoriasis patients and 11 ankylosing spondylitis. FindingsOur study revealed altered immune signatures of specific myeloid and lymphocyte subsets in blood and skin, both in terms of cell numbers and gene expression. Specifically, we discovered elevated proportions of circulating CD14++ monocytes, increased expression of major histocompatibility complex (MHC) class II molecule by circulating CD16+ monocytes, as well as increased expression of genes related to skin homing and to pro-inflammatory responses in psoriasis by circulating plasmacytoid dendritic cells (pDCs). Circulating CD8+ T effector memory cells in psoriasis patients exhibited reduced abundance but increased skin-homing potential. In psoriatic lesions, we observed a hyperinflammatory myeloid-cell state and enrichment of IL17-producing cells with a tissue-resident memory T-cell signature. InterpretationThe changes in immune cell numbers and gene expression indicate a significant alteration in the immune landscape of psoriasis patients. This suggests that the immune system in psoriasis is reprogrammed, affecting both innate and adaptive branches. These findings provide new insights into the aberrant immune-cell signatures in the circulation and skin lesions in psoriasis, and thereby help to understand its pathophysiology. FundingThis study was financially supported by the National Natural Science Foundation of China (U23A6012), Science and Technology Planning Project of Guangzhou (2024A03J0055, 202206080005), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202204).

systems biology↗

bioRxiv2021

Interactions of host defense and hyper-keratinization in psoriasis

ObjectivesTo understand the crosstalk between the host and microbiota in psoriatic skin, using a systems biology approach based on transcriptomics and microbiome profiling. MethodsWe collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions, and the associations between the host defense and microbiota dynamic. ResultsWe found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using coexpression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a "core" set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the "core network" of genes. ConclusionsWe identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition.

systems biology↗