Abstract
Interleukin-31 has been implicated in the pathophysiology of multiple
atopic disorders such as atopic dermatitis (AD), rhinitis and airway
hyperreactivity. In AD, IL-31 has been identified as one of the main
‘drivers’ of its cardinal symptom pruritus. Here, we aim to 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-produced cytokines including
IL-31, thereby mediating inflammatory responses, initiating
immunoregulatory circuits, and stimulating itch and neuronal outgrowth
through activation of the heterodimer receptor IL-31 receptor alpha
(IL31RA)/Oncostatin M receptor β. IL31RA expression is found on human
and murine dorsal root ganglia neurons, epithelial cells including
keratinocytes as well as various 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
signaling may be a beneficial approach for various inflammatory diseases
including prurigo nodularis. For example, 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.
Key words: Interleukin-31, Interleukin-31 receptor A,
Oncostatin M receptor, atopic dermatitis, neuroinflammation.