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-kappaB 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.

Del Cornò, M., Michienzi, A., Masotti, A., Da Sacco, L., Bottazzo, G., Belardelli, F., et al. (2009). CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells. BLOOD, 114(4), 796-806 [10.1182/blood-2009-01-199406].

CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells

MICHIENZI, ALESSANDRO;
2009-07-23

Abstract

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-kappaB 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.
23-lug-2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/13 - BIOLOGIA APPLICATA
English
Con Impact Factor ISI
th1 cells; cells, cultured; down-regulation; lipopolysaccharides; humans; dendritic cells; poly i-c; tumor necrosis factor-alpha; cell polarity; interferon-beta; rna, messenger; imidazoles; interleukin-10; toll-like receptors; chemokine ccl2; drug combinations
Del Cornò, M., Michienzi, A., Masotti, A., Da Sacco, L., Bottazzo, G., Belardelli, F., et al. (2009). CC chemokine ligand 2 down-modulation by selected Toll-like receptor agonist combinations contributes to T helper 1 polarization in human dendritic cells. BLOOD, 114(4), 796-806 [10.1182/blood-2009-01-199406].
Del Cornò, M; Michienzi, A; Masotti, A; Da Sacco, L; Bottazzo, G; Belardelli, F; Gessani, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/10545
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