Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology, director of clinical research and patch testing, George Washington University School of Medicine and Health Sciences, discusses the involvement of the JAK/STAT pathway in the pathogenesis of atopic dermatitis.
JAK1 and in some cases JAK2 have been shown to play mediating roles in signaling various extracellular cytokines that contribute to the pathogenesis of atopic dermatitis, said Jonathan Silverberg, MD, PhD, MPH, associate professor of dermatology and director of clinical research and patch testing at George Washington University School of Medicine and Health Sciences.
How is the JAK/STAT pathway involved in the pathogenesis and/or mediation of atopic dermatitis?
The JAK/STAT pathway is involved potentially in the pathogenesis of atopic dermatitis in several different ways. When we think about the various cytokines that have been implicated in atopic dermatitis, there are many. There's interleukin (IL)-13, IL-4, IL-31, TSLP [thymic stromal lymphopoietin], IL-22, etc. These are all extracellular cytokines, extracellular signals, that in order for them to work and have an effect intracellularly they have to bind to receptors and then something has to pass that signal into the cell. The JAKs, the Janus kinases, are those signals.
So, in particular, JAK1 and, to some extent, JAK2 play important roles in mediating the signals of those different cytokines that I just mentioned. The thought process is rather than just targeting a single cytokine, we could potentially block the signaling of multiple cytokines by blocking the JAKs from transducing those signals for the different cytokines.