Increased expression of chemokines DC-CK1, ELC and TARC by dendritic cells and in synovium from patients with rheumatoid arthritis

Background

Dendritic cells (DCs) are the professional antigen-presenting cells that produce a large set of chemokines. Recent evidence suggests that DCs, by their production of chemokines, are important in the inflammatory cascade.

Objective

The aim of the study was to evaluate the expression of chemokines by DCs and synovial tissue from patients with RA in comparison with that from healthy individuals.

Methods

Immature and mature DCs were obtained using standardized protocols as described previously. The expression of the chemokines DC-CK1, ELC, IL-8, MIP-1a, SDF-1a, SDF-1a, lymphotactin, SLC, MIP-3a, TARC and MDC in iDCs, mDCS and synovial tissue was determined by using real-time quantitative RT-PCR techniques (PRISM).

Results

iDCs of RA patients (n = 10) express low levels of ELC and MIP-1a, and high levels of MDC and TARC, which were equal when compared with DCs from healthy individuals (n = 8). However, the expression of DC-CK1 (P < 0.001) and IL-8 (P = 0.02) by iDCs from RA patients was significantly higher. After full maturation, expressions of DC-CK1 (P < 0.001), ELC (P < 0.001), IL-8 (P = 0.02), MIP-1a (P < 0.001) and TARC (P < 0.001) were significantly higher in DCs from RA patients relative to healthy donors. In RA synovial tissue, DC-CK1 (230-fold), ELC (400-fold) and IL-8 (36-fold) were expressed at much higher levels when compared with healthy individuals. TARC was also expressed at higher levels in RA synovial tissue but this failed to achieve significance.

Conclusion

In DCs both from patients with RA and in biopsies of rheumatoid synovium, significantly higher levels of DC-CK1, ELC and IL-8 mRNA are present relative to their normal counterparts. MIP-1a and TARC were expressed at higher levels exclusively by DCs from RA. These results suggest that DC-CK1, ELC, MIP-1a and TARC, along with DCs, play a critical role in RA.