Differential production of IL-23 and IL-12 by myeloid-derived dendritic cells in response to TLR agonists.

Abstract

The recently delineated role for IL-23 in enhancing Th-17 activity suggests that regulation of its expression is distinct from that of IL-12. We hypothesized that independent TLR-mediated pathways are involved in the regulation of IL-12 and IL-23 production by myeloid-derived dendritic cells (DCs). The TLR 2 ligand, lipoteichoic acid (LTA), the TLR 4 ligand, LPS, and the TLR 7/8 ligand, resimiquod (R848), induced production of IL-23 by DCs. None of these TLR ligands alone induced significant IL-12 production, except when combined with IFN-gamma or other TLR ligands. Notably, IL-23 production in response to single TLR ligands was inhibited by IL-4. DCs treated with single TLR agonists induced IL-17A production by allogeneic and Ag-specific memory CD4(+) T cells, an effect that was abrogated by IL-23 neutralization. Moreover, these DCs stimulated IL-17A production by tumor peptide-specific CD8(+) T cells. In contrast, DCs treated with dual signals induced naive and memory Th1 responses and enhanced the functional avidity of tumor-specific CD8(+) T cells. These results indicate that distinct microbial-derived stimuli are required to drive myeloid DC commitment to IL-12 or IL-23 production, thereby differentially polarizing T cell responses.

• Authors: Robert E Roses, Shuwen Xu, Min Xu, Ursula Koldovsky, Gary Koski, Brian J Czerniecki
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 7 Pg. 5120-7 (Oct 01 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 18802116 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Imidazoles
• Interleukin-17
• Interleukin-23
• Ligands
• Lipopolysaccharides
• Teichoic Acids
• Toll-Like Receptors
• Interleukin-12
• lipoteichoic acid
• Interferon-gamma
• resiquimod

Topics

• Cell Differentiation (drug effects, immunology)
• Cell Movement (drug effects, immunology)
• Cells, Cultured
• Coculture Techniques
• Dendritic Cells (cytology, drug effects, immunology, metabolism)
• Humans
• Imidazoles (pharmacology)
• Interferon-gamma (biosynthesis, pharmacology)
• Interleukin-12 (biosynthesis)
• Interleukin-17 (biosynthesis)
• Interleukin-23 (biosynthesis, genetics, metabolism)
• Ligands
• Lipopolysaccharides (pharmacology)
• Myeloid Cells (cytology, drug effects, immunology, metabolism)
• Teichoic Acids (pharmacology)
• Toll-Like Receptors (agonists)