Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages

Takashi Hashimoto, Christina Dorothy Kursewicz, Rachel Alison Fayne, Sonali Nanda, Serena Maya Shah, Leigh Nattkemper, Hiroo Yokozeki, Gil Yosipovitch

Research output: Contribution to journalArticle

Abstract

Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the troublesome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of the generation of IL-31. In SD lesions, dermal infiltrating IL-31(+) cells were increased in number compared with the healthy controls, and the majority of IL-31(+) cells were CD68(+) macrophages. The presence of itch in SD was significantly associated with the amount of CD68(+)/IL-31(+) macrophages and CD68(+)/CD163(+) M2 macrophages. The number of CD68(+)/IL-31(+) macrophages was correlated with the number of dermal C-C chemokine receptor type 4(+) T helper type 2 cells, IL-17(+) cells, basophils, substance P(+) cells, and dermal deposition of periostin and hemosiderin. Furthermore, murine peritoneal macrophages expressed an M2 marker arginase-1 and generated IL-31 when stimulated with a combination of substance P, periostin, and red blood cell lysate (representing hemosiderin). IL-31 from macrophages may play a role in itch in SD.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StateAccepted/In press - Jan 1 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Hashimoto, T., Kursewicz, C. D., Fayne, R. A., Nanda, S., Shah, S. M., Nattkemper, L., Yokozeki, H., & Yosipovitch, G. (Accepted/In press). Mechanisms of Itch in Stasis Dermatitis: Significant Role of IL-31 from Macrophages. Journal of Investigative Dermatology. https://doi.org/10.1016/j.jid.2019.09.012