International Immunology, Vol. 13, No. 8, 1053-1061,
August 2001
© 2001 Japanese Society for Immunology
IL-1ß induces dendritic cells to produce IL-12
Barbara Ann Karmanos Cancer Institute of Wayne State University, Detroit, MI 48201, USA
Correspondence to: A. Galy
The cytokine IL-12, a product of dendritic cells (DC), plays a major role in cellular immunity, notably by inducing lymphocytes to produce IFN-
. Microbial products, T cell signals and cytokines induce the production of IL-12. Here, IL-1ß is identified as a new IL-12-inducing agent, acting conjointly with CD40 ligand (CD40L) on human monocyte-derived DC in vitro. The effects of IL-1ß were dose dependent, specifically blocked by neutralizing antibodies, and were observed both in immature and mature DC. Immature DC secreted more IL-12 than mature DC, but the effects of IL-1ß were not due to a block of DC maturation as determined by analysis of DC surface markers. The mechanisms of action of IL-1ß could be contrasted to that of other inducers of IL-12 such as IFN- and lipopolysaccharide (LPS). Either IL-1ß or IFN- co-induced IL-12 with CD40L but conjointly, IL-1ß, CD40L and IFN- synergized, inducing very high levels of IL-12. The effects of IL-1ß differed from those of LPS in that IL-1ß, unlike LPS, could not induce IL-12 solely after IFN- priming; and when combined with CD40L, IL-1ß, unlike LPS, induced little IL-10. The mechanism of action of IL-1ß involves IL-12
mRNA up-regulation, and we show that the combination of CD40L and IL-1ß induces high levels of IL-12 and IL-12ß mRNA in DC. Altogether, these results delineate a new mechanism linking adaptive and innate immune responses for the regulation of IL-12 production in DC and for the role of IL-1ß in the development of cellular immunity.
Keywords: CD40 ligand, cytokines, dendritic cells, human, IL-1, IL-12, IL-10, lipopolysaccharide
Transmitting editor: G. Trinchieri
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