Ovol1 regulates psoriasis-like skin inflammation and epidermal hyperplasia. Ovol1 regulates psoriasis-like skin inflammation and epidermal hyperplasia

Psoriasis is a common inflammatory skin disease characterized by aberrant inflammation and epidermal hyperplasia. Molecular mechanisms that regulate psoriasis-like skin inflammation remain to be fully understood. Here we show that the expression of Ovol1 transcription factor is upregulated in psoriatic skin, and its deletion results in aggravated psoriasis-like skin symptoms following stimulation with imiquimod (IMQ). Using bulk and single-cell RNA-sequencing, we identify molecular changes in the epidermal, fibroblast and immune cells of Ovol1-deficient skin that reflect altered course of epidermal differentiation and enhanced inflammatory responses. Furthermore, we provide evidence for excessive full-length IL-1 signaling in the microenvironment of IMQ-treated Ovol1-deficient skin that functionally contributes to immune cell infiltration and epidermal hyperplasia. Collectively, our study uncovers a protective role for Ovol1 in curtailing psoriasis-like inflammation and the associated skin pathology Overall design: Droplet-based single cell RNA-seq experiments were performed to identify molecular differences between control and Ovol1 null in untreated and imiquimod (IMQ) treated adult murine back skin.

银屑病（Psoriasis）是一类常见的炎症性皮肤病，以异常炎症反应与表皮增生为典型特征。目前，调控类银屑病皮肤炎症的分子机制尚未完全阐明。本研究发现，Ovol1转录因子（transcription factor）在银屑病皮损中表达上调；而该基因的缺失会加重咪喹莫特（imiquimod, IMQ）刺激诱导的类银屑病皮肤症状。通过批量RNA测序与单细胞RNA测序技术，本研究鉴定了Ovol1缺失皮肤中表皮细胞、成纤维细胞与免疫细胞的分子变化，这些变化反映了表皮分化进程的改变与炎症反应的增强。此外，本研究证实，经IMQ处理的Ovol1缺失皮肤微环境中存在过度激活的全长IL-1信号通路，该通路在功能上促进了免疫细胞浸润与表皮增生。综上，本研究揭示了Ovol1在抑制类银屑病炎症及相关皮肤病理进程中的保护作用。
整体实验设计：本研究开展基于液滴的单细胞RNA测序实验，用于鉴定未处理与经咪喹莫特（IMQ）处理的成年小鼠背部皮肤中，对照组与Ovol1纯合缺失组之间的分子差异。