Details

Autor(en) / Beteiligte

• Lim, Hui Xuan
• Hong, Hye-Jin
• Jung, Mi Young
• Cho, Daeho
• Kim, Tae Sung

Titel

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

Ist Teil von

• Cytokine (Philadelphia, Pa.), 2013-08, Vol.63 (2), p.179-186

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •Dendritic cells (DCs) of mice lacking IL-12p40 and/or IL-18 were compared.•Deficiency of IL-12p40 and/or IL-18 in DCs showed similar surface phenotypes.•IL-12p40/IL-18-deficient DCs showed decreased IL-10 production.•IL-12p40- and IL-12p40/IL-18-deficient DCs impaired Th1 and Th17 differentiation.•IL-12p40 is more crucial than IL-18 in inducing Th1 and Th17 differentiation. 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.