IL-27 Production and Regulation in Human Dendritic Cells Treated with the Chemical Sensitizer NiSO4.

Abstract

Allergic contact dermatitis (ACD) is a major cause of occupational skin disease, and nickel is among the most prevalent contact allergens. Dendritic cells (DC) play an important role in ACD and in the type of the ensuing immune response through differential phenotypes and cytokine production. The interleukin (IL)-12 cytokine family is composed of heterodimeric cytokines sharing homology at the subunit, receptors and signaling levels. We previously showed that nickel can upregulate the production of IL-12p40 and IL-23, both known to be pro-inflammatory. In this work, we aimed to extend our knowledge on nickel regulation of the IL-12 cytokine family by focusing on IL-27, a recently identified immunomodulatory cytokine from this family. We showed that nickel induced the production of IL-27 in human monocyte-derived DC (MoDC), regulating IL-22 production by human CD4+ T cells. We also showed that nickel was able to induce the expression of the two subunits of IL-27: il-27p28 and ebi3. Furthermore, we demonstrated that the production of IL-27 was dependent on the TLR4, p38 MAPK, NF-κB, and Jak-STAT signaling. However, IL-27 subunits were differentially regulated by these pathways. Indeed, both subunits were positively regulated by the TLR4 and NF-κB pathways, but only il-27p28 was also dependent on p38 MAPK and Jak-STAT pathways. Our results contribute to a better understanding of nickel-induced ACD by focusing on the IL-12 cytokine family and elucidating the mechanism of IL-27 regulation in human dendritic cells.