TY - JOUR
T1 - CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells
AU - Del Cornò, Manuela
AU - Michienzi, Alessandro
AU - Masotti, Andrea
AU - Da Sacco, Letizia
AU - Bottazzo, Gian Franco
AU - Belardelli, Filippo
AU - Gessani, Sandra
PY - 2009
Y1 - 2009
N2 - Toll-like receptor (TLR) signaling activation by pathogens is critical to the induction of immune responses, and demands tight regulation.We describe in this study that CC chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (DCs). Impaired CCL2 secretion occurs concomitantly to interleukin-12 up-regulation, being part of a complex regulatory circuit ensuring optimal T helper type 1 polarization. Interestingly, triggering selected TLRs or their combinations differently affects nuclear factor-κB p65 activation and microRNA expression. Overall, these results indicate that CCL2 supplies an important immunomodulatory role to DCs, and may contribute to dictate the cytokine profile in T helper type 1 responses induced by DCs.
AB - Toll-like receptor (TLR) signaling activation by pathogens is critical to the induction of immune responses, and demands tight regulation.We describe in this study that CC chemokine ligand 2 (CCL2) secretion triggered by TLR4 or TLR8 engagement is strongly inhibited upon simultaneous activation of both TLRs in human monocyte-derived dendritic cells (DCs). Impaired CCL2 secretion occurs concomitantly to interleukin-12 up-regulation, being part of a complex regulatory circuit ensuring optimal T helper type 1 polarization. Interestingly, triggering selected TLRs or their combinations differently affects nuclear factor-κB p65 activation and microRNA expression. Overall, these results indicate that CCL2 supplies an important immunomodulatory role to DCs, and may contribute to dictate the cytokine profile in T helper type 1 responses induced by DCs.
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U2 - 10.1182/blood-2009-01-199406
DO - 10.1182/blood-2009-01-199406
M3 - Article
C2 - 19465691
AN - SCOPUS:68249161285
VL - 114
SP - 796
EP - 806
JO - Blood
JF - Blood
SN - 0006-4971
IS - 4
ER -