4.6 Article

Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta

Journal

EXPERIMENTAL DERMATOLOGY
Volume 30, Issue 6, Pages 804-810

Publisher

WILEY
DOI: 10.1111/exd.14279

Keywords

IL-31; IL-31 receptor; itch; oncostatin M; prurigo nodularis

Categories

Funding

  1. Kiniksa Pharmaceuticals, Corp.

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The study revealed a close correlation between itch intensity and the expression of interleukin-31, its receptors, and oncostatin M in prurigo nodularis. IL-31 and OSM may stimulate dermal cells expressing IL-31RA and OSMR beta, contributing to itch and inflammation in PN. This complex cytokine/receptor network could be a potential therapeutic target for PN-associated itch.
Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN-associated itch is difficult because its aetiology is still unknown. This study aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)-31, its receptor complex components IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMR beta), and oncostatin M (OSM), which is a ligand of OSMR beta, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL-31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL-31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMR beta (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL-31 were T cells (27.0% of total IL-31-expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL-31RA-expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMR beta was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL-31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL-31RA and OSMR beta (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN-associated itch.

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