Interleukin-31: The 'itchy' cytokine in inflammation and therapy.

The cytokine interleukin-31 has been implicated in the pathophysiology of multiple atopic disorderssuch asatopic dermatitis (AD), allergic rhinitisand airway hyperreactivity. 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. TH 2 cells play a central role in AD and release high levels ofTH 2-associated cytokines including IL-31,thereby mediating inflammatory responses, initiating immunoregulatory circuits, stimulating itch and neuronal outgrowth through activation ofthe heterodimeric receptor IL-31 receptor alpha (IL31RA)/Oncostatin M receptor (OSMRβ). IL31RA expression is found onhumanand murine dorsal root ganglia neurons, epithelial cells including keratinocytes as well asvarious innate immune cells. IL-31 is a critical cytokine involved in neuro-immune 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 signalingmay 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.