Activation of eosinophils by IL-12 family cytokine IL-27: Implications of the pleiotropic roles of IL-27 in allergic responses

Shuiqing Hu, Chun Kwok Wong, Christopher Wai Kei Lam

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Interleukin (IL)-27 is a novel IL-12 family cytokine and its immunomodulatory effects on T-lymphocytes, B-lymphocytes and mast cells were extensively studied. IL-27 could suppress Th2-mediated allergic diseases in mouse models. However, the role of IL-27 on eosinophils, the principal effector cells in allergic diseases, remains unexplored. Our present study revealed that eosinophils constitutively express functional IL-27 receptor heterodimer, gp130 and WSX-1. IL-27 could prolong eosinophil survival by reducing apoptosis, modulate the expression of adhesion molecules to facilitate eosinophil adhesion and accumulation, and induce the release of proinflammatory cytokines IL-6, tumor necrosis factor-α, IL-1β and chemokines CCL2, CXCL8 and CXCL1. The stimulation effects of IL-27 on eosinophils could not be abrogated by Th2 cytokine IL-25, hematopoietic cytokine granulocyte macrophage colony-stimulating factor, and toll-like receptor 4 ligand lipopolysaccharide (LPS). These findings are different from the effects of IL-27 and LPS on monocytes. Intracellular signaling mechanistic studies showed that IL-27-mediated eosinophil activation was differentially regulated by the activation of extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, as well as nuclear factor-κB. Based on the above results, IL-27 could play crucial roles in allergic diseases by the activation of eosinophils via differential intracellular signaling cascades. According to the present findings of its activating effects on human eosinophils, IL-27 may play pleiotropic roles in human allergic responses.

Original languageEnglish (US)
Pages (from-to)54-65
Number of pages12
JournalImmunobiology
Volume216
Issue number1-2
DOIs
StatePublished - Jan 1 2011

Keywords

  • Apoptosis
  • Chemokines
  • Cytokines
  • Eosinophils
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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