Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus

Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively.BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs.Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE.Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by autoreactive T and B cells [1,2]. Dendritic cells (DCs), the most effective antigen-presenting cells (APCs), are capable of activating na？ve T cells and initiating T-cell responses. DCs have been hypothesized to play an important role in the pathogenesis of SLE [3,4].DCs are developed in the bone marrow (BM), released into the circulation, and subsequently home to many tissues. The function of DCs varies according to their stage of maturity. Immature DCs are capable of capturing and processing antigens (Ags). After migration to the lymphoid organs, where they become mature, their ability to captu