Interleukin-21 inhibits dendritic cell activation and maturation

• Published in: Blood Vol. 102; no. 12; pp. 4090 - 4098
• Main Authors: Brandt, Katja, Bulfone-Paus, Silvia, Foster, Donald C., Rückert, René
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.12.2003; The Americain Society of Hematology
• Subjects: Animals; Antigen Presentation; Biological and medical sciences; Bone Marrow Cells; Cell Differentiation - drug effects; Cell Movement; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Drug Interactions; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Interleukin-15 - pharmacology; Interleukins - pharmacology; Lipopolysaccharides - pharmacology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Modulation of the immune response (stimulation, suppression); T-Lymphocytes - immunology; Dendritic cell; Vertebrata; Mammalia; Immune response; Mouse; Antigen presenting cell; Animal; Rodentia; Cytokine; Interleukin 21; Immune regulation; Interleukin 15
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-03-0669

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 γ 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. (Blood. 2003;102: 4090-4098)