Interleukin-10 Influenced Differentiation And Function Of Human Dendritic Cells

Background: Dendritic Cell (DC) are key regulator in immune responses, capable of priming naive resting T cells and initiating primary T-cell responses when pulsed with antigenic peptides or proteins. In vitro, DC can be generated from human CD34⁺ bone marrow, cord blood, peripheral blood progenitor cells and CD14⁺ blood monocytes after culture with different cytokine combinations including granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), and either interleukin-4 (IL-4) or tumor necrosis factor-a (TNF-a). Defects in T-cell function observed in SLE may result from underlying defects in the function of DC. Recent studies indicate that DC and several cytokines are implicated in the induction of autoimmune diseases. Phenotypic and functional abnormalities have been described in dendritic cells from patients with lupus. Lupus-derived serum contains factors capable of inducing the differentiation and activation of normal DC.Study design and Methods: To investigate the association between interleukin-10,DC and the pathogenesis of SLE. Serum levels of interleukin-10,interferon-αand interleukin-6 in patients with systemic lupus erythematosus (SLE) and healthy persons were assessed by an enzyme-linked immunosorbent assay (ELISA). SLEDAI score, the level of anti-dsDNA antibody, complement component C3,C4 and 24 hours urine protein level were also collected. Two distinct origins were used to induced DC: monocyte derived-DC(MDDC) and cord blood(CD34⁺ hematopoietic stem cell) derived-DC(CDDC). In the induction process of monocyte derived-DC, interleukin-10 concentration 30pg/ml was added. Cord blood derived-DC was treated by high level of interleukin-10 SLE serum, except interferon-αand interleukin-6. The phenotypes of DC(HLA-DR,CD80,CD86,CD1a, et al) were analyzed by flow cytometer and the stimulating allogenic T lymphocytes proliferation abilities of these DC were checked by CCK-8. ELISA was used to measure the IL-12p40,IL-10 and INF-γconcentration of the MDDC and CDDC culture supernatants. The percentage of CD3⁺CD8^+/-TNF-γ^+/- and CD3⁺CD8^+/-IL-10^+/- in mixed lymphocyte reaction(MLR) were detected by flow cytometer.Results: Serum level of IL-10 was higher in SLE patients. Cultured MDDC with high level of IL-10, at the concentration of 30pg/ml, there were lower level of HLA-DR,CD86,CD80,CD83 compared with 0pg/ml IL-10 level. 30pg/ml IL-10 treated MDDC showed decreased abilities of stimulating allogenic T cell proliferation. The IL-12p40,IL-10 and INF-γconcentration of the MDDC culture supernatants were no significantly alteration. There were no statistic significance between groups among the high level of IL-10 concentration SLE serum treatedCDDC.Conclusion: Exogenous IL-10 shows a possible relationship between thiscytokine on the differentiation and function of MDDC. Serum level ofIL-10 suggests no relationship between these cytokine in thedifferentiation and function of CDDC. So relation between IL-10 and DCin the pathogenesis of SLE needs further research.