Skip to main content
. 2021 Feb 10;8:639097. doi: 10.3389/fmed.2021.639097

Figure 1.

Figure 1

IL-31 signaling bridges the gap between the immune system, neurons and epithelial surfaces. During T cell activation DOCK8 dissociates from EPAS1 enabling EPAS1 to translocate to the nucleus. Within the nucleus EPAS1 forms a complex with SP1 initiating IL31 transcription. TH2 cells are a major source of IL-31 production. In IL-31RA/OSMRß-expressing sensory neurons IL-31 induces the activation of ion channels (TRPV1, TRPA1) and transmits pruritus signals via BNP to the CNS. Moreover, IL-31 stimulates neuronal growth and the branching of sensory nerves. Furthermore, IL-31 targets immune cells such as mast cells, eosinophils, basophils and monocytes/dendritic cells to induce inflammation. Within the skin, IL-31 impairs keratinocyte differentiation as well as barrier function and in turn activates keratinocytes to produce cytokines, chemokines and pruritus mediators amplifying skin inflammation and itch. Interestingly, IL-31 also interacts with dermal fibroblasts initiating tissue remodeling by inducing collagen production and cytokine as well as chemokine expression. Hence, IL-31 signaling exerts pleiotropic effects beyond pruritus.