Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 09 1 16 EN Yahya Asemani Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Ezzatifar Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran AND Department of Immunology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran Mohammad Kamalinejad Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran Ali Anissian Department of Veterinary, Abhar Branch, Islamic Azad University, Abhar, Iran Masoud Tohidfar Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran Forouzan Karimi Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2026 05 25 2026 07 03 Irritant contact dermatitis (ICD) is a common inflammatory skin disorder characterized by epidermal barrier disruption and dysregulated inflammatory responses, yet its molecular basis remains incompletely understood. To identify conserved transcriptional alterations associated with ICD, we performed an integrated cross-species transcriptomic analysis of human and murine Gene Expression Omnibus datasets generated using microarray and RNA sequencing platforms. Genes were prioritized using a π-value–based ranking strategy integrating expression effect size and statistical significance, followed by orthology mapping, functional enrichment, and protein–protein interaction network analyses. A total of 174 prioritized genes were shared across all datasets, forming a conserved cross-species transcriptomic signature associated with ICD. The shared signature comprised increased expression of inflammatory and barrier-associated genes, including S100A8, S100A9, SERPINB3 and SERPINB4, KRT6A, and GJB2, together with mitotic regulators, such as CDK1, CDC20, and AURKB, whereas differentiation- and homeostasis-associated regulators, including GATA3, RORA, and LRP4, were consistently reduced. Functional enrichment identified mitotic cell-cycle processes, chromosome segregation, and Aurora kinase–related pathways, as the dominant biological themes, together with cornified envelope formation, while network analysis prioritized CDK1, CDC20, AURKB, and BIRC5 among the principal hub genes. Collectively, these findings identify a conserved ICD-associated transcriptomic program consistent with keratinocyte hyperproliferation, impaired epidermal differentiation, barrier remodeling, and innate inflammatory responses. Although requiring independent experimental validation, this conserved signature provides a framework for future mechanistic studies and for the development of candidate biomarkers in irritant-induced skin inflammation. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4854 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4854/2437