loading page

Interleukin-31: The ‘itchy’ cytokine in inflammation and therapy
  • +2
  • Angeliki Datsi,
  • Majid Alam,
  • Fareed Ahmad,
  • Martin Steinhoff,
  • Joerg Buddenkotte
Angeliki Datsi
Universittaetsklinikum Duesseldorf
Author Profile
Majid Alam
Hamad Medical Corporation
Author Profile
Fareed Ahmad
Hamad Medical Corporation
Author Profile
Martin Steinhoff
Weill Cornell Medicine Qatar
Author Profile
Joerg Buddenkotte
Hamad Medical Corporation
Author Profile

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.

Peer review status:ACCEPTED

26 Nov 2020Submitted to Allergy
27 Nov 2020Submission Checks Completed
27 Nov 2020Assigned to Editor
27 Nov 2020Reviewer(s) Assigned
05 Dec 2020Review(s) Completed, Editorial Evaluation Pending
06 Dec 2020Editorial Decision: Revise Minor
27 Jan 20211st Revision Received
16 Feb 2021Submission Checks Completed
16 Feb 2021Assigned to Editor
16 Feb 2021Reviewer(s) Assigned
17 Feb 2021Review(s) Completed, Editorial Evaluation Pending
17 Feb 2021Editorial Decision: Accept