Frontiers in Immunology (Nov 2023)

Oncostatin M suppresses IL31RA expression in dorsal root ganglia and interleukin-31-induced itching

  • Masataka Suehiro,
  • Tomofumi Numata,
  • Ryo Saito,
  • Nozomi Yanagida,
  • Chie Ishikawa,
  • Kazue Uchida,
  • Tomoko Kawaguchi,
  • Yuhki Yanase,
  • Yozo Ishiuji,
  • John McGrath,
  • Akio Tanaka

DOI
https://doi.org/10.3389/fimmu.2023.1251031
Journal volume & issue
Vol. 14

Abstract

Read online

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intermittent itchy rash. Type 2 inflammatory cytokines such as interleukin (IL)-4, IL-13, and IL-31 are strongly implicated in AD pathogenesis. Stimulation of IL-31 cognate receptors on C-fiber nerve endings is believed to activate neurons in the dorsal root ganglion (DRG), causing itch. The IL-31 receptor is a heterodimer of OSMRβ and IL31RA subunits, and OSMRβ can also bind oncostatin M (OSM), a pro-inflammatory cytokine released by monocytes/macrophages, dendritic cells, and T lymphocytes. Further, OSM expression is enhanced in the skin lesions of AD and psoriasis vulgaris patients.ObjectiveThe current study aimed to examine the contributions of OSM to AD pathogenesis and symptom expression.MethodsThe expression levels of the OSM gene (OSM) and various cytokine receptor genes were measured in human patient skin samples, isolated human monocytes, mouse skin samples, and mouse DRG by RT-qPCR. Itching responses to various pruritogens were measured in mice by counting scratching episodes.ResultsWe confirmed overexpression of OSM in skin lesions of patients with AD and psoriasis vulgaris. Monocytes isolated from the blood of healthy subjects overexpressed OSM upon stimulation with IL-4 or GM-CSF. Systemic administration of OSM suppressed IL31RA expression in the mouse DRG and IL-31-stimulated scratching behavior. In contrast, systemic administration of OSM increased the expression of IL-4- and IL-13-related receptors in the DRG.ConclusionThese results suggest that OSM is an important cytokine in the regulation of skin monocytes, promoting the actions of IL-4 and IL-13 in the DRG and suppressing the action of IL-31. It is speculated that OSM released from monocytes in skin modulates the sensitivity of DRG neurons to type 2 inflammatory cytokines and thereby the severity of AD-associated skin itch.

Keywords