Dataset Information

PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells.

ABSTRACT: Prostaglandin E(2) (PGE(2)) is an inflammatory mediator often used to increase CCR7 expression in the dendritic cells (DCs) used as cancer vaccines and to enhance their responsiveness to lymph node-associated chemokines. Here, we show that high surface expression of CCR7 on PGE(2)-matured DCs is associated with their suppressed production of the endogenous CCR7 ligand, CCL19, and is reversible by exogenous CCL19. In contrast to the PGE(2)-matured DCs, DCs matured in the presence of toll-like receptor (TLR) ligands and interferons produce high levels of both CCL19 and CCR7 mRNA/protein, but show selectively reduced expression of surface CCR7, which is compensated after DC removal from the CCL19-rich maturation environment. In accordance with these findings, PGE(2)-matured DCs show significantly higher in vitro migratory responsiveness to lymph node-associated chemokines directly after DC generation, but not after additional short-term culture in vitro, nor in vivo in patients injected with (111)indium-labeled DCs. The differences in CCL19-producing ability imprinted during DC maturation result in their different abilities to attract CCR7(+) naive T cells. Our data help to explain the impact of PGE(2) on CCR7 expression in maturing DCs and demonstrate a novel mechanism of regulatory activity of PGE(2), mediated by the inhibition of DCs ability to attract naive T cells.

SUBMITTER: Muthuswamy R

PROVIDER: S-EPMC2938836 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells.

Muthuswamy Ravikumar R Mueller-Berghaus Jan J Haberkorn Uwe U Reinhart Todd A TA Schadendorf Dirk D Kalinski Pawel P

Blood 20100524 9

Prostaglandin E(2) (PGE(2)) is an inflammatory mediator often used to increase CCR7 expression in the dendritic cells (DCs) used as cancer vaccines and to enhance their responsiveness to lymph node-associated chemokines. Here, we show that high surface expression of CCR7 on PGE(2)-matured DCs is associated with their suppressed production of the endogenous CCR7 ligand, CCL19, and is reversible by exogenous CCL19. In contrast to the PGE(2)-matured DCs, DCs matured in the presence of toll-like rec ...[more]

PMID: 20498301

Similar Datasets

Project description:BackgroundThe non-signalling chemokine receptors, including receptors DARC, D6 and CCX-CKR, have recently been shown to be involved in chemokine clearance and activity regulation. The human chemokine receptor CRAM (also known as HCR or CCRL2) is the most recently identified member of this atypical group. CRAM is expressed on B cells in a maturation-stage dependent manner and absent on T cells. We have recently shown that it competitively binds CCL19. CCL19 and its signalling receptor CCR7 are critical components involved in cell recruitment to secondary lymphoid organs and in maturation. B cell Chronic Lymphocytic Leukemia (B-CLL) is a low-grade lymphoma characterized by proliferative centres (or pseudofollicles). Proliferative centres develop due to abnormal cellular localisation and they are involved in the development of malignant cells. CCR7 is highly expressed on B cells from CLL patients and mediates migration towards its ligands CCL19 and CCL21, while CRAM expression and potential interferences with CCR7 are yet to be characterized.ResultsIn this study, we show that B cells from patients with B-CLL present highly variable degrees of CRAM expression in contrast to more consistently high levels of CCR7. We investigated the hypothesis that, similar to the atypical receptor DARC, CRAM can modulate chemokine availability and/or efficacy, resulting in the regulation of cellular activation. We found that a high level of CRAM expression was detrimental to efficient chemotaxis with CCL19. MAP-kinase phosphorylation and intracellular calcium release induced by CCL19 were also altered by CRAM expression. In addition, we demonstrate that CRAM-induced regulation of CCL19 signalling is maintained over time.ConclusionsWe postulate that CRAM is a factor involved in the fine tuning/control of CCR7/CCL19 mediated responses. This regulation could be critical to the pivotal role of CCL19 induced formation of proliferation centres supporting the T/B cells encounter as well as disease progression in B-CLL.

Dataset Information

PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells.

Publications

PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets