0000000001110284
AUTHOR
Melanie Fassbender
Cyclic adenosine monophosphate and IL-10 coordinately contribute to nTreg cell-mediated suppression of dendritic cell activation
In humans and mice naturally occurring regulatory T cells (nTregs) are crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Here we show that co-culture of murine dendritic cells (DC) and nTregs results in an immediate increase of cAMP in DC, responsible for a rapid down-regulation of co-stimulatory molecules (CD80, CD86). In addition, the inhibitory surface molecule B7-H3 on DC is up-regulated. Subsequently, nTreg-derived IL-10 inhibits the cytokine production (IL-6, IL-12) of suppressed DC therewith preserving their silent phenotype. Hence, our data indicate that nTreg…
Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo.
Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signaling pathways, we wondered if the simultaneous activation of these signaling cascades would synergize with respect to DC activation and induce superior cytotoxic T-lymphocyte (CTL) activity in vivo. We observed that indeed the combined activation of MyD88-dependent and -independent signaling induced by TLR7 and TLR3 ligands provoked a more rapid and more sustained bone marrow–der…