176 C10orf99/2610528A11Rik induces keratinocyte proinflammatory response and regulates lipid metabolism and barrier formation of the skin

The protective machinery of the skin opposes external agents by barrier and innate adaptive immunity. local interplay in epithelial-immune microenvironment (EIME) contributes to situation-specific protective/inflammatory responses, its dysregulation generates inflammatory loops atopic dermatitis psoriasis. Keratinocytes are key player EIME. However, a common regulator keratinocyte response this has not yet been identified. To address issue, we analyzed specimens from four animal models for microarray. We found that expression levels one orphan gene, 2610528A11Rik, were up all models. Protein human ortholog, C10orf99, much higher lesional or psoriasis than healthy skin. RNA-Seq analyses normal epidermal keratinocytes (NHEKs) transfected with C10orf99-expressing plasmids revealed their increased proinflammatory transcriptional response, gene ontology suggested highest relation “Lipid/cholesterol biosynthesis,” “Cadherin/cell adhesion,” “Mitochondrion.” Furthermore, transcription factor (TF) enrichment analysis only pathway activating SREBP1, TF regulating sterol synthesis, was significantly impaired NHEKs. Moreover, treatment 3D-cultured epidermis C10orf99 synthetic peptides during stratification downregulated filaggrin loricrin dose-dependent manner. Our results suggest 2610528A11Rik/C10orf99 can be master induces regulates formation