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Papers of the Week

Papers: 27 Feb 2021 - 5 Mar 2021


2021 Feb 24


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


Datsi A, Steinhoff M, Ahmad F, Alam M, Buddenkotte J
Allergy. 2021 Feb 24.
PMID: 33629401.


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. T 2 cells play a central role in AD and release high levels ofT 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.