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

Del Cornò M, Michienzi A, Masotti A, Da Sacco L, Bottazzo GF, Belardelli F, Gessani S.
Blood. 2009 Jul 23;114(4):796-806. Epub 2009 May 22.

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.

URL: http://bloodjournal.hematologylibrary.org/cgi/reprint/114/4/796

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/19465691

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