Predicting Skin Sensitizer Potency and Immune Response Using UISS-TOX: A Novel Approach for Assessing Allergenic Potential

The aim of this study was to explore the sensitizing potency of several known skin allergens, focusing on their capacity to induce allergic contact dermatitis (ACD). Our approach involves different bioinformatic tools, including UISS-TOX, a simulation platform designed to predict the immune response following allergen exposure. Using eight well-characterized skin sensitizers, including pyridine and hexyl salicylate, we evaluated docking interactions with keratin and Toll-like receptors (TLRs), and we predicted B-cell epitopes, providing insights into potential antigenic sites. The results were integrated into UISS-TOX simulations to observe T helper cell and cytokine dynamics over time. The simulations revealed distinct Th1-mediated responses consistent with ACD, enabling not only the prediction of skin sensitizer potency but also the differentiation of response intensities among the sensitizers. Pyridine, for instance, demonstrated a higher Th1 activation and associated cytokine release than hexyl salicylate, aligning with its stronger sensitizing profile in literature. This study underscores UISS-TOX’s potential as a reliable in silico method for allergenicity prediction, aligning with New Approach Methodologies and reducing the need for animal testing.