Interleukin-31: The itchy cytokine in inflammation and therapy

The 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. T(H)2 cells play a central role in AD and release high levels of T(H)2-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 (OSMR beta). 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/OSMR beta axis appears to be a promising approach for inflammatory, neuroinflammatory, and pruritic disorders in the future.

Automated summary

Interleukin-31 (IL-31) plays a critical role in various atopic disorders, particularly in atopic dermatitis (AD), by modulating inflammatory responses, stimulating itch, and promoting neuronal outgrowth through the IL-31 receptor A/Oncostatin M receptor (IL31RA/OSMR beta) axis. Inhibition of IL-31 downstream signaling shows promise for future therapies targeting inflammatory, neuroinflammatory, and pruritic disorders.