Published online May 19, 2008
doi:10.1084/jem.20071450
The Journal of Experimental Medicine, Vol. 205, No. 6, 1447-1461
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Gerosa et al.
Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells
Franca Gerosa1,
Barbara Baldani-Guerra1,
Lyudmila A. Lyakh2,
Giovanna Batoni3,
Semih Esin3,
Robin T. Winkler-Pickett2,
Maria Rita Consolaro1,
Mario De Marchi4,
Daniela Giachino4,
Angela Robbiano4,
Marco Astegiano5,
Angela Sambataro6,
Robert A. Kastelein7,
Giuseppe Carra1, and
Giorgio Trinchieri2
1 Department of Pathology, Section of Immunology, University of Verona, 37134 Verona, Italy
2 Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702
3 Department of Experimental Pathology, Medical Biotechnology, Infectivology and Epidemiology, University of Pisa, 56126 Pisa, Italy
4 Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Italy
5 Gastroenterology Unit, Azienda Sanitaria Ospedaliera San Giovanni Battista, 10126 Torino, Italy
6 Gastroenterology Unit, Azienda Sanitaria Ospedaliera San Luigi, 10043 Orbassano, Italy
7 Discovery Research, Schering-Plough Biopharma, Palo Alto, CA 94304
CORRESPONDENCE Franca Gerosa: franca.gerosa{at}univr.it
We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand β-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) 
strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by β-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor β, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4+ T cells, IL-1β, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection.
Abbreviations used: MALP-2, 2-kD macrophage-activating lipopeptide; MDP, muramyl dipeptide; mono-DC, monocyte-derived DC; NOD2, nucleotide-binding oligodimerization domain; PRR, pattern recognition receptor; TLR, Toll-like receptor.
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