Objectives: Dendritic cells (DCs) play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Reduced numbers of blood DCs and the accumulation of DCs at inflammatory sites have been observed in SLE. One crucial feature of DCs is their ability to migrate. We analyzed thematuration/activation state and the migratory capacity of different DC precursor subsets in SLE to further elucidate their role in autoimmunity.
Methods: Plasmacytoid DCs (pDCs), myeloid DCs (mDCs) and monocytes from SLE patients, healthy volunteers, and healthy volunteers immunized with tetanus/diphtheria were examined by flow cytometry for expression of subset specific antigens (BDCA-2, CD11c, CD14, HLA-DR), activation/maturation markers (CD83, CD86, CD40, BLyS) and chemokine receptors (CCR1, CCR5, CCR7, ChemR23). Additionally, migratory capacity to chemokine receptors was investigated in vitro using the chemokines RANTES, CCL19 and chemerin.
Results: SLE monocytes and myeloid DCs had higher CD86 (p=0.04) and BLyS expression levels (p=0.0008). ChemR23 expression was lower in SLE plasmacytoid (p = 0.004) and myeloid DCs (p = 0.03). Basal (p= 0.004) and CCL19-specific migration levels (p=0.004) were higher in SLE plasmacytoid DCs. Altered DC function in SLE had no correlative changes in chemokine receptor expression whereas immunization-induced blood DC migration patterns in healthy donors were accompanied by changes in chemokine receptor expression.
Conclusions: The phenotypic and migratory disturbances observed in SLE blood DCs could result in altered distribution of DCs in peripheral tissues, contributing to dysregulated immune responses and autoimmunity.