Article Text
Abstract
Objective: To assess whether DC from RA produce altered cytokine levels and whether this is regulated by triggering of Fc gamma receptors (FcγR).
Methods: The production of proinflammatory (TNFα, IL1, IL6), Th1 (IL12, IFNγ), and Th2 (IL10) cytokine profiles of immature DC (iDC) from patients with RA and healthy subjects upon triggering of FcγR dependent and independent pathways was investigated. iDC, derived from blood monocytes by standardised protocols, were stimulated with immune complexes (IC) at day 6 for 48 hours and, subsequently, for 2 days with LPS in the presence or absence of IC or IFNγ, resulting in fully matured DC (mDC). IL1, IL6, TNFα, IFNγ, IL12, and IL10 levels in supernatants were measured by ELISA and RIA.
Results: mDC from patients with RA showed a markedly increased production of IL1, IL6, TNFα, and IL10 compared with DC from healthy donors. Triggering of FcγR decreased the production of proinflammatory cytokines IL1, IL12, and IFNγ by iDC and mDC in RA and controls. The production of IL6 and TNFα decreased in patients with RA, whereas it was increased in controls. Triggering of FcγR independent mechanisms using IFNγ increased the production of proinflammatory and Th1 cytokines, which was more pronounced in RA.
Conclusion: FcγR dependent pathways influence cytokine production by DC. A skewed balance towards proinflammatory and Th1 cytokines in RA can, at least partly, be restored by triggering FcγR on DC in RA. Insight into the mechanism which determines the FcγR balance might lead to new strategies to abrogate Th1 driven inflammatory processes in RA.
- dendritic cells
- Fc gamma receptor
- tumour necrosis factor
- interleukin 10
- interleukin 12
- DC, dendritic cells
- ELISA, enzyme linked immunosorbent assay
- FACS, fluorescence activated cell sorter
- FcγR, Fc gamma receptor
- HAGGS, heat aggregated gamma immunoglobulins
- IC, immune complexes
- iDC, immature dendritic cells
- IFNγ, interferon γ
- IL, interleukin
- LPS, lipopolysaccharide
- mDC, mature dendritic cells
- RA, rheumatoid arthritis
- RIA, radioimmunoassay
- TNFα, tumour necrosis factor α