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Comparative Study
. 2008 Oct 1;181(7):5120-7.
doi: 10.4049/jimmunol.181.7.5120.

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

Robert E Roses  1 , Shuwen Xu, Min Xu, Ursula Koldovsky, Gary Koski, Brian J Czerniecki
Affiliations
Comparative Study

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

VSports - Robert E Roses et al. J Immunol. .

"VSports手机版" 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 VSports手机版. 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. .

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