Potential autocrine regulation of interleukin-33/ST2 signaling of dendritic cells in allergic inflammation

Z Su, J Lin, F Lu, X Zhang, L Zhang, N B Gandhi, C S de Paiva, S C Pflugfelder, D-Q Li

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

This study identified a novel phenomenon that dendritic cells (DCs) produced interleukin (IL)-33 via Toll-like receptor (TLR)-mediated innate pathway. Mouse bone marrow-derived DCs were treated with or without microbial pathogens or recombinant murine IL-33. IL-33 mRNA and protein were found to be expressed by DCs and largely induced by several microbial pathogens, highly by lipopolysaccharide (LPS) and flagellin. Using two mouse models of topical challenge by LPS and flagellin and experimental allergic conjunctivitis, IL-33-producing DCs were observed in ocular mucosal surface and the draining cervical lymph nodes in vivo. The increased expression levels of myeloid differentiation primary-response protein 88 (MyD88), nuclear factor (NF)-κB1, NF-κB2, and RelA accompanied by NF-κB p65 nuclear translocation were observed in DCs exposed to flagellin. IL-33 induction by flagellin was significantly blocked by TLR5 antibody or NF-κB inhibitor quinazoline and diminished in DCs from MyD88 knockout mice. IL-33 stimulated the expression of DC maturation markers, CD40 and CD80, and proallergic cytokines and chemokines, OX40L, IL-4, IL-5, IL-13, CCL17 (C-C motif chemokine ligand 17), TNF-α (tumor necrosis factor-α), and IL-1β. This stimulatory effect of IL-33 in DCs was significantly blocked by ST2 antibody or soluble ST2. Our findings demonstrate that DCs produce IL-33 via TLR/NF-κB signaling pathways, suggesting a molecular mechanism by which local allergic inflammatory response may be amplified by DC-produced IL-33 through potential autocrine regulation.

Original languageEnglish (US)
Pages (from-to)921-30
Number of pages10
JournalMucosal Immunology
Volume6
Issue number5
DOIs
StatePublished - Sep 2013

Keywords

  • Animals
  • Antibodies, Blocking/administration & dosage
  • Autocrine Communication
  • Cell Differentiation
  • Cells, Cultured
  • Conjunctivitis, Allergic/immunology
  • Cytokines/metabolism
  • Dendritic Cells/drug effects
  • Flagellin/immunology
  • Gene Expression Regulation/drug effects
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein
  • Lipopolysaccharides/immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Mucous Membrane/immunology
  • Myeloid Differentiation Factor 88/genetics
  • NF-kappa B/antagonists & inhibitors
  • Quinazolines/administration & dosage
  • Receptors, Interleukin/immunology
  • Signal Transduction/drug effects
  • Toll-Like Receptor 5/immunology
  • Transcription Factor RelA/genetics

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