AbstractThe cytokine interleukin‐31 has been implicated in the pathophysiology of multiple atopic disorders such as atopic dermatitis (AD), allergic rhinitis, and airway hyper‐reactivity. In AD, IL‐31 has been identified as one of the main “drivers” of its cardinal symptom, pruritus. Here, we summarize the mechanisms by which IL‐31 modulates inflammatory and allergic diseases. TH2 cells play a central role in AD and release high levels of TH2‐associated cytokines including IL‐31, thereby mediating inflammatory responses, initiating immunoregulatory circuits, stimulating itch, and neuronal outgrowth through activation of the heterodimeric receptor IL‐31 receptor A (IL31RA)/Oncostatin M receptor (OSMRβ). IL31RA expression is found on human and murine dorsal root ganglia neurons, epithelial cells including keratinocytes and various innate immune cells. IL‐31 is a critical cytokine involved in neuroimmune communication, which opens new avenues for cytokine modulation in neuroinflammatory diseases including AD/pruritus, as validated by recent clinical trials using an anti‐IL‐31 antibody. Accordingly, inhibition of IL‐31‐downstream signaling may be a beneficial approach for various inflammatory diseases including prurigo. However, as to whether downstream JAK inhibitors directly block IL‐31‐mediated‐signaling needs to be clarified. Targeting the IL‐31/IL31RA/OSMRβ axis appears to be a promising approach for inflammatory, neuroinflammatory, and pruritic disorders in the future.