JAK-STAT pathway and JAK inhibitors: a primer for dermatologists

Abstract

Background: All cellular events depend upon the DNA synthesis and gene expression involving complex interplay between ligands such as interleukins and interferons, with various cell membrane receptors. These ligand-receptors interactions transmit signals within the cell via numerous signal transduction pathways to affect gene expression. Janus kinase/signal transducer and activator of transcription pathway (JAK-STAT) are one of these pathways involved in the pathogenesis of various inflammatory and immunologic diseases. The therapeutic inhibition of this pathway has yielded promising results in many cutaneous and systemic disorders. It should be noted that, there are 4 JAK proteins and 7 STAT proteins. Currently, the first and second generations of JAK inhibitors are used for different indications, while more selective and pan-JAK inhibitors are under research. Methods: we searched PubMed, Scopus, Cochrane library and Embase as search engines. The terms used to find the useful and appropriate articles were, “JAK-STAT pathway, janus kinase inhibitors and JAK-STAT inhibitors in dermatology". Results: This article has summarized the different components of the JAK-STAT pathway, their regulation, classification of JAK inhibitors, and their adverse effects. Conclusion: Based on the encouraging results of many ongoing clinical trials, their indications have been extended to various autoimmune dermatologic conditions in recent years.