The JAK-Cytokine Interface – A Review and Update on Prospective Clinical Considerations

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David Hashemi
Neal Bhatia


JAK inhibitor, janus kinase, atopic dermatitis, psoriasis, alopecia areata, vitiligo


Janus kinases (JAKs) are non-receptor tyrosine kinases that work together with signal transducers and activators of transcription (STAT) proteins to form the JAK/STAT pathway. Together, this pathway is responsible for mediating a wide range of downstream cytokines and growth factors, and inhibition of various components of this pathway has been a major area of research focus in recent years. Each of the major enzymes of the family – which include JAK1, JAK2, JAK3, and Tyrosine Kinase 2 (TYK2) – or combinations of JAKs is responsible for its own set of most strongly-associated inflammatory mediators, and inhibition of specific JAKs or combination of JAKs can therefore also potentially allow for modulation of specific inflammatory factors and their associated conditions. To date, JAK inhibitors have particularly been studied in the treatment of atopic dermatitis (felt to be primarily driven by IL-4, IL-13, and IL-5), psoriasis (IL-12/IL-23), alopecia areata (IL-2, IL-15, and IFN-γ), and vitiligo (IL-15 and IFN-γ), given that these factors can all be found downstream of specific JAK/STAT pathways as shown in Figure 1. By providing a concise review of the inflammatory factors affected by each JAK, this article aims to support clinicians as they engage in the ever-growing body of research around the use of JAK inhibitors for potential treatment of dermatologic conditions.


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