Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells

Hubertus Hochrein, Meredith O'Keeffe, Thomas Luft, Stéphane Vandenabeele, Raelene J. Grumont, Eugene Maraskovsky, Ken Shortman

Research output: Contribution to journalArticleResearchpeer-review

306 Citations (Scopus)

Abstract

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon γ effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.

Original languageEnglish
Pages (from-to)823-833
Number of pages11
JournalJournal of Experimental Medicine
Volume192
Issue number6
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Granulocyte/macrophage colony-stimulating factor
  • Homodimeric interleukin 12
  • Interferon γ
  • T helper type 1
  • T helper type 2

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