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Triggering of FcGR during dendritic cell maturation leads to a decreased expression of the chemokines DC-CK1, ELC and TARC

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Introduction

Dendritic cells (DCs) determine the balance between tolerance and immunity in which Fc γ receptors (FcγR) are thought to play a decisive role. Previously, we found that DCs from RA patients expressed a different FcγR profile.

Objective

The aim of the study was to determine the potential difference in chemokine expression and production between DC from RA patients and healthy controls upon FcγR mediated triggering.

Methods

Immature and mature DC were obtained using standardized protocols as described recently. The expressions of the chemokines DC-CK1, ELC, IL-8, MIP-1a, TARC and MDC were determined by using real-time quantitative RT-PCR techniques (PRISM). The production of DC-CK1 was confirmed by using ELISA techniques. Triggering of FcγR was achieved by the addition of heat aggregated IgG immunoglobulins (HAGGS) to the culture for 48 hours.

Results

Stimulation of FcγR resulted in a significantly decreased expression of DC-CK1 (35%), ELC (50%), IL-8 (640%) and TARC (39%) by DC from RA patients (n = 6). Although not significant, the same trend was observed for MIP-1a (160%). In contrast, a significant increase was seen for DC-CK1 (300%), ELC (120%), IL-8 (640%), MIP-1a (160%) and TARC (39%) upon triggering of FcγR on DC from healthy individuals (n = 5). MDC was the only chemokine that showed a decrease upon FcγR dependent stimulation of DC in both groups. By using ELISA techniques, we confirmed these data for DC-CK1 on the protein level. Triggering of FcγR led to a decreased (63%) production of DC-CK1 by DC from RA patients, whereas an increase (137%) was observed by those from controls.

Conclusion

Our study lends strong support for a skewed FcγR balance toward the inhibitory subtype in RA, and shows the critical role for FcγR in the inhibition of chemokine production by DCs. Furthermore, our data show that FcγR triggering influences Toll-like receptor (LPS) mediated cell responses.

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Radstake, T., van der Voort, R., Figdor, C. et al. Triggering of FcGR during dendritic cell maturation leads to a decreased expression of the chemokines DC-CK1, ELC and TARC. Arthritis Res Ther 6, 48 (2004) doi:10.1186/ar1090

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Keywords

  • Dendritic Cell
  • Decisive Role
  • Cell Maturation
  • Mediate Cell
  • Dendritic Cell Maturation