Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Clin Transl Med. 2022 Dec;12(12):e976. doi: 10.1002/ctm2.976.
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.
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.
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.
We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin.
银屑病的确切发病机制仍不完全清楚。我们旨在通过基于转录组学和微生物组分析的系统生物学方法，更好地理解银屑病的潜在机制。
我们收集了 13 名银屑病患者、15 名银屑病关节炎患者和 12 名强直性脊柱炎患者的皮损和非皮损皮肤的组织活检和拭子。为了研究这三种情况之间分子谱的相似性和差异性，以及宿主防御和微生物群落组成之间的关联，我们进行了高通量 RNA 测序以定量组织中的基因表达谱。通过聚类扩增子序列并计数为操作分类单元，对局部皮肤部位的 16S 宏基因组组成进行定量。我们进一步分析了转录组和微生物组分析之间的关联。
我们发现皮损和非皮损样本在转录谱方面存在显著差异。差异表达基因的功能注释显示，中性粒细胞激活的主要富集。通过使用共表达基因网络，我们确定了一个与活检部位局部银屑病严重程度相关的基因模块。从这个模块中，我们发现了一组与中性粒细胞激活、表皮细胞分化和对细菌的反应功能相关的“核心”基因。皮肤微生物组分析显示， Enhydrobacter、Micrococcus 和 Leptotrichia 的丰度与核心网络中的基因显著相关。
我们确定了一个与局部疾病严重程度和微生物组组成相关的核心基因网络，该网络涉及银屑病皮肤的炎症和过度角化。
