IL-33-activated dendritic cells induce an atypical TH2-type response

Matthew A. Rank, Takao Kobayashi, Hideaki Kozaki, Kathleen R. Bartemes, Diane L. Squillace, Hirohito Kita

Research output: Contribution to journalArticlepeer-review

265 Scopus citations


Background: IL-33, a recently discovered IL-1 family cytokine, is implicated in the development of TH2-type responses in vivo. However, the cellular targets for IL-33 are poorly understood. Objective: We tested the hypotheses that dendritic cells (DCs) respond to IL-33 and that IL-33-activated DCs prime naive CD4+ T cells to produce TH2-type cytokines. Methods: Dendritic cells were derived from mouse bone marrow, and their expression of the IL-33 receptor, ST2, was examined by fluorescence-activated cell sorting and real-time RT-PCR. The DCs' responses to IL-33 were examined by fluorescence-activated cell sorting (MHC-II and CD86 expression) and by ELISA (IL-6 and IL-12 production). The ability of IL-33-activated DCs to prime naive T cells was assessed by coculture with isolated CD4+ T cells and by measuring cytokines in the supernatants. Results: ST2 mRNA was detectable in highly purified DCs. ST2 protein was abundant within DCs, but was barely detectable on their cell surfaces. Incubation of DCs with IL-33 increased their expression of MHC-II and CD86 and production of IL-6, but IL-12 was not produced. Anti-ST2 antibody inhibited IL-6 production from IL-33-activated DCs by approximately 60%; anti-ST2 did not affect IL-6 production from LPS-activated DCs. When incubated with naive CD4+ T cells alone, IL-33 failed to stimulate cytokine production. In contrast, naive CD4+ T cells incubated with IL-33-activated DCs showed robust production of IL-5 and IL-13, but IL-4 and IFN-γ were undetectable. Conclusion: Dendritic cells respond directly to IL-33 through ST2. The IL-33 and DC interaction may represent a new pathway to initiate TH2-type immune responses.

Original languageEnglish (US)
Pages (from-to)1047-1054
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number5
StatePublished - May 2009


  • IL-33
  • T2 cytokines
  • allergy
  • dendritic cells
  • inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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