Exploring the role of Janus kinase (JAK) in atopic dermatitis: a review of molecular mechanisms and therapeutic strategies

Recent studies have demonstrated that Janus kinase (JAK) plays a crucial role in signal transduction by directly affecting various cytokine receptors involved in inflammatory diseases such as atopic dermatitis (AD). Large-scale clinical trials on AD utilizing JAK inhibitors and biologic reagents, such as dupilumab, which targets the IL-4Rα receptor subunit of the Th2 cytokines IL-4 and IL-13, have yielded highly favorable results in comparison to traditional therapies. This indicates that therapeutic strategies based on molecular biology are efficacious in clinical settings. However, in September 2021, the U.S. Food and Drug Administration (FDA) indicated that tofacitinib, a JAK inhibitor, may carry various risks, including severe heart disease. Similar concerns have been raised for other JAK inhibitors, and further safety evaluations are underway. Thus, human biology involving JAKs appeared more complicated than we expected. In this article, we provide an overview of the molecular mechanisms of AD and examine the molecular targeting drugs for AD from the perspective of JAK-related biology.