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

被引：21

作者：

Del Corno, Manuela ^{[1
]}

Michienzi, Alessandro ^{[1
]}

Masotti, Andrea ^{[2
]}

Da Sacco, Letizia ^{[2
]}

Bottazzo, Gian Franco ^{[2
]}

Belardelli, Filippo ^{[1
]}

Gessani, Sandra ^{[1
]}

机构：

[1] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy

[2] Childrens Hosp Bambino Gesu, Lab Gene Express Microarrays, Rome, Italy

来源：

BLOOD | 2009年 / 114卷 / 04期

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; NF-KAPPA-B; PERIPHERAL-BLOOD MONOCYTES; GRANULOMA-FORMATION; BETA-CHEMOKINES; IMMUNE-SYSTEM; HIV-1; GP120; IFN-BETA; EXPRESSION; INDUCTION;

D O I：

10.1182/blood-2009-01-199406

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-kappa B 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. (Blood. 2009; 114: 796-806)

引用

页码：796 / 806

页数：11

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