Functional interleukin-33 receptors are expressed in early progenitor stages of allergy-related granulocytes

Hirofumi Tsuzuki, Yojiro Arinobu, Kohta Miyawaki, Ayako Takaki, Shun Ichiro Ota, Yuri Ota, Hiroki Mitoma, Mitsuteru Akahoshi, Yasuo Mori, Hiromi Iwasaki, Hiroaki Niiro, Hiroshi Tsukamoto, Koichi Akashi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Interleukin-33 (IL-33) induces T helper type 2 (Th2) cytokine production and eosinophilia independently of acquired immunity, leading to innate immunity-mediated allergic inflammation. Allergy-related innate myeloid cells such as eosinophils, basophils and mast cells express the IL-33 receptor (IL-33R), but it is still unknown how IL-33 regulates allergic inflammation involving these cells and their progenitors. Here, we revealed that the functional IL-33R was expressed on eosinophil progenitors (EoPs), basophil progenitors (BaPs) and mast cell progenitors (MCPs). In the presence of IL-33, these progenitors did not expand, but produced a high amount of Th2 and pro-inflammatory cytokines such as IL-9, IL-13, IL-1β and IL-6. The amount of cytokines produced by these progenitors was greater than that by mature cells. In vivo, IL-33 stimulated the expansion of EoPs, but it was dependent upon the elevated serum IL-5 that is presumably derived from type 2 innate lymphoid cells that express functional IL-33R. These data collectively suggest that EoPs, BaPs and MCPs are not only the sources of allergy-related granulocytes, but can also be sources of allergy-related cytokines in IL-33-induced inflammation. Because such progenitors can differentiate into mature granulocytes at the site of inflammation, they are potential therapeutic targets in IL-33-related allergic diseases.

Original languageEnglish
Pages (from-to)64-73
Number of pages10
JournalImmunology
Volume150
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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