Interleukin-21 inhibits dendritic cell activation and maturation.
Interleukin 21 (IL-21) is a newly described cytokine with homology to IL-4 and IL-15. They belong to a cytokine family that uses the common gamma chain for signaling but also have their private high-affinity receptors. Since it is well known that IL-4 modulates differentiation and activation of dendritic cells (DCs), we analyzed effects of IL-21 compared with IL-15 on DC differentiation, maturation, and function. Here we show that DCs generated with granulocyte-macrophage colony-stimulating factor (GMCSF) in the presence of IL-21 (IL-21DCs) differentiated into phenotypically and functionally altered DCs characterized by reduced major histocompatibility complex class II (MHCII) expression, high antigen uptake, and low stimulatory capacity for T-cell activation in vitro. Additionally, IL-21DCs completely failed to induce antigen (Ag)-specific T-cell mediated contact hypersensitivity. Furthermore, IL-21 blocked lipopolysaccharide (LPS)-induced activation and maturation of DCs, which was not mediated by release of the anti-inflammatory cytokine IL-10. In contrast, when supplementing GMCSF with IL-15, DCs differentiated into mature antigen-presenting cells (APCs) with low antigen uptake and highly significant increased capacities to stimulate T cells in vitro and in vivo. Taken together, these results identify a dichotomous action of these structurally related cytokines on DCs, establishing IL-21 as inhibitory cytokine on DC activation and IL-15 as potent stimulator of DC function, making both cytokines interesting targets for therapeutic manipulation of DC-induced immune reactions.
Brandt
Katja
K
Research Center Borstel, Dept of Immunology and Cell Biology, Parkallee 22, 23845 Borstel, Germany.
Bulfone-Paus
Silvia
S
Foster
Donald C
DC
Rückert
René
R
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D004347:Drug Interactions; D019409:Interleukin-15 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D000098546:Interleukin-21
D019409:Interleukin-15; D007378:Interleukins; D008070:Lipopolysaccharides; D000098546:Interleukin-21