Interleukin (IL)-4 is a major regulatory cytokine governing bioactive IL-12 production by mouse and human dendritic cells

• Published in: The Journal of experimental medicine Vol. 192; no. 6; pp. 823 - 834
• Main Authors: Hochrein, H, O'Keeffe, M, Luft, T, Vandenabeele, S, Grumont, R J, Maraskovsky, E, Shortman, K
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 18.09.2000
• Subjects: Animals; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Humans; Interferon-gamma - pharmacology; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Interleukin-4 - pharmacology; Lipopolysaccharides - pharmacology; Mice; Mice, Inbred C57BL; Monocytes - immunology; Original; Recombinant Proteins - pharmacology; Spleen - immunology; T-Lymphocytes - immunology; Thymus Gland - immunology
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.192.6.823

Interleukin (IL)-12 may be secreted as a bioactive T helper type 1 (Th1) cell-inducing heterodimer, as a monomer, or as an antagonistic homodimer. We analyzed the IL-12 produced by mouse splenic dendritic cells (DCs), human thymic DCs, and cultured human monocyte-derived DCs. IL-12 production required both a microbial or T cell-derived stimulus and an appropriate cytokine milieu. The different IL-12 forms were differentially regulated by the cytokines present rather than the stimulus used. IL-4 alone or together with granulocyte/macrophage colony-stimulating factor or interferon gamma effectively enhanced the production of the bioactive heterodimer and selectively reduced the antagonistic homodimer of IL-12. Therefore, IL-4, the major Th2-driving cytokine, provides a negative feedback causing DCs to produce the major Th1-inducing cytokine, bioactive IL-12.