Principal role of IL-12p40 in the decreased Th1 and Th17 responses driven by dendritic cells of mice lacking IL-12 and IL-18

Hui Xuan Lim, Hye Jin Hong, Mi Young Jung, Dae Ho Cho, Tae Sung Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

IL-12 and IL-18 are cytokines which are mainly secreted by endothelial cells and monocytes including dendritic cells. The well-known effects of IL-12 and IL-18 in the protection against bacteria and virus infection as well as tumor development are associated with their characteristics in synergistically driving the development of T helper type 1 (Th1) cells and inducing IFN-γ production. In this study, we compared the knockout effects of IL-12 and/or IL-18 genes on phenotypes and functional capabilities of dendritic cells (DCs) including their ability to polarize naive CD4+ T cells. The expression levels of surface molecules such as MHC II, CD80, CD86 and ICOSL, and endocytic capacity were not significantly differences between DCs of wild type (WT) mice and double knockout (DKO) mice of IL-12p40 and IL-18. Additionally, DCs lacking IL-12p40 and/or IL-18 genes were equivalently efficient in inducing T cell proliferation, compared with the WT-DCs. Interestingly, IL-10 production significantly decreased in DKO-DCs, while production of other inflammation-related cytokines were unaffected in WT-DCs and DKO-DCs. Importantly, IL-12p40-/--DCs and DKO-DCs severely impaired the ability to induce IFN-γ and IL-17 production from CD4+ T cells. IL-18-/--DCs also moderately decreased IL-17 production and IL-17-expressing CD4+ T cells when co-cultured with CD4+ T cells, demonstrating the involvement of IL-18 in driving IL-17 differentiation. Taken together, these results suggest the principal contribution of IL-12p40 in inducing Th1 and Th17 polarization, regardless of similar surface phenotypes of DCs.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalCytokine
Volume63
Issue number2
DOIs
Publication statusPublished - 2013 Aug 1

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Keywords

  • Dendritic cells
  • IL-12
  • IL-18
  • Th1
  • Th17

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

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