Physiological itch is crucial for host defense because scratching behavior leads to removing potentially harmful organism from the skin. However, itch in chronic disease such as atopic dermatitis induces unpleasant effects. Recent studies have paid attention to type2 cytokines including IL-4, IL-13 and IL-31 as allergic dermatitis-associated itch mediators. Indeed, receptors of these cytokines are expressed on dorsal root ganglion neurons and the cytokines can activate and/or sensitize the neurons directly. However, immune regulation of itch sensation has not yet been fully understood.
IL-27 is an immunoregulatory cytokine which belongs to IL-12 cytokine family. IL-27 is mainly produced by antigen-presenting cells and transmits the signals via a heterodimeric receptor composed of IL-27 receptor a chain (WSX-1) and gp130. Although IL-27 suppresses Th2 and ILC2 responses, the role of IL-27 in neural system remains to be elucidated.
Here, we found that mice deficient in WSX-1 showed enhanced scratching behavior against several pruritogens. Conversely, administration of recombinant IL-27 suppressed pruritogen-induced scratching behavior in WT mice. This suppressive effect of IL-27 in itch sensation is abolished in Nav1.8-Cre WSX-1^flox/flox mice which lack sensory neuron specific WSX-1 expression. In addition, treatment with JAK kinase inhibitor abrogates the effect of IL-27 in scratching behavior. These results imply that IL-27 acts on sensory neuron and suppresses neuronal activity by JAK kinase-dependent manner, leading to regulatory function in itch sensation.