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

Immunology. 2017 Jan;150(1):64-73. doi: 10.1111/imm.12667. Epub 2016 Sep 30.

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.

Keywords: basophils; cytokines; eosinophils; haematopoiesis; mast cells.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Gene Expression Regulation
  • Granulocyte Precursor Cells / immunology*
  • Granulocytes / immunology*
  • Hypersensitivity / immunology*
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33 / immunology*
  • Interleukin-5 / genetics
  • Interleukin-5 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Interleukin / metabolism*
  • Th2 Cells / immunology*

Substances

  • Cytokines
  • Il1rl1 protein, mouse
  • Il33 protein, mouse
  • Inflammation Mediators
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-5
  • Receptors, Interleukin

Associated data

  • GENBANK/GSE76385