Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33

Blood. 2009 Feb 12;113(7):1526-34. doi: 10.1182/blood-2008-05-157818. Epub 2008 Oct 27.

Abstract

In mice, interleukin-18 (IL-18) regulates Th1- or Th2-type immune responses depending on the cytokine environment and effector cells involved, and the ST2-ligand, IL-33, primarily promotes an allergic phenotype. Human basophils, major players in allergic inflammation, constitutively express IL-18 receptors, while ST2 surface expression is inducible by IL-3. Unexpectedly, freshly isolated basophils are strongly activated by IL-33, but, in contrast to mouse basophils, do not respond to IL-18. IL-33 promotes IL-4, IL-13 and IL-8 secretion in synergy with IL-3 and/or FcepsilonRI-activation, and enhances FcepsilonRI-induced mediator release. These effects are similar to that of IL-3, but the signaling pathways engaged are distinct because IL-33 strongly activates NF-kappaB and shows a preference for p38 MAP-kinase, while IL-3 acts through Jak/Stat and preferentially activates ERK. Eosinophils are the only other leukocyte-type directly activated by IL-33, as evidenced by screening of p38-activation in peripheral blood cells. Only upon CD3/CD28-ligation, IL-33 weakly enhances Th2 cytokine expression by in vivo polarized Th2 cells. This study on primary human cells demonstrates that basophils and eosinophils are the only direct target leukocytes for IL-33, suggesting that IL-33 promotes allergic inflammation and Th2 polarization mainly by the selective activation of these specialized cells of the innate immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophils / cytology
  • Basophils / immunology*
  • CD28 Antigens / metabolism
  • CD3 Complex / metabolism
  • Cell Communication / immunology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Complement C5a / metabolism
  • Eosinophils / cytology
  • Eosinophils / immunology*
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / metabolism
  • Hypersensitivity / pathology
  • Interleukin-1 / metabolism
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-13 / metabolism
  • Interleukin-18 / metabolism
  • Interleukin-3 / metabolism
  • Interleukin-33
  • Interleukin-4 / metabolism
  • Interleukin-8 / metabolism
  • Interleukins / immunology
  • Interleukins / metabolism*
  • Leukotriene C4 / metabolism
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Receptors, Cell Surface / metabolism
  • Signal Transduction / immunology
  • Solubility
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • CD28 Antigens
  • CD3 Complex
  • IL1RL1 protein, human
  • IL33 protein, human
  • IL4 protein, human
  • Interleukin-1
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-13
  • Interleukin-18
  • Interleukin-3
  • Interleukin-33
  • Interleukin-8
  • Interleukins
  • Receptors, Cell Surface
  • Interleukin-4
  • Leukotriene C4
  • Complement C5a