Interferon-alpha and interleukin-6 in SLE serum induce the differentiation and maturation of dendritic cells derived from CD34+ hematopoietic precursor cells.

The objective of this study was to investigate the effects of the cytokines IFN-alpha, IL-6 and IL-10 present in the serum of systemic lupus erythematosus (SLE) patients on the differentiation and maturation of DCs derived from CD34(+) hematopoietic precursor cells (HPCs). CD34(+) HPCs cultured in SLE serum containing elevated levels of IFN-alpha or IL-6 differentiated into DCs showing an increased expression of HLA-DR, CD80 and CD86, decreased IL-12 secretion along with increased IL-10 production, and an increased ability to stimulate allogenic T-cell proliferation, compared with DCs cultured in normal serum. DCs cultured with high levels of IFN-alpha increased the proportion of both CD3(+)CD8(-)IFN-gamma(+) and CD3(+)CD8(+)IFN-gamma(+) T-cell subsets, and increased the production of IFN-gamma in the allogenic MLR. DCs cultured with high levels of IL-6 decreased the proportion of both IFN-gamma(+) T-cell subsets, and decreased the secretion of IFN-gamma, but increased the production of IL-10. The IL-10 present in SLE serum did not significantly alter the phenotype or function of the DCs. IFN-alpha and IL-6 present in SLE serum induce CD34(+) HPCs to differentiate into DCs with different regulatory effects on T-cell differentiation, which might be involved in the initiation and maintenance of SLE. Copyright (c) 2010 Elsevier Ltd. All rights reserved.