Preclinical evaluation of Janus Kinase inhibitors in atopic dermatitis: Insights from an oxazolone-induced mouse model

Abstract Atopic dermatitis (AD) is a prevalent inflammatory skin condition affecting a substantial proportion of the population. However, the lack of robust preclinical evidence of Janus kinase (JAK) inhibitors in AD treatment necessitates the development of more effective therapies, including those repurposed from other indications. Thus, we aimed to establish a preclinical evaluation system targeting JAK inhibitors to explore their effectiveness and mechanism of action in AD mouse model. We utilized an oxazolone (OXA)-induced AD mouse model to assess the effects of JAK inhibitors. Ear thickness, IgE and MPO levels were measured regularly. At the end of study, spleen weights were measured, and ear tissues were processed for cytokine analysis and pathological evaluation. Additionally, flow cytometry was utilized to analyze immune cells in auricular draining lymph nodes (DLN). Following OXA challenge, temporal changes in the immune system were observed, characterized by increased pro-inflammatory cytokines, immune cell infiltration in auricular DLN, and elevated IgE and MPO levels. Treatment with JAK inhibitors led to a reduction in AD-associated features and resulted in decreased immune cell infiltration and alterations in specific molecular features. Our study successfully established a preclinical mouse model for AD, facilitating a comprehensive understanding of skin inflammation, immunomodulation, and the pharmacodynamics of test articles in the context of AD.