Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is characterized by a systemic autoimmune response with profound and diverse T cell changes. Dendritic cells (DCs) are important orchestrators of immune responses and have an important role in the regulation of T cell function. The objective of this study was to determine whether myeloid DCs from individuals with SLE display abnormalities in phenotype and promote abnormal T cell function. Monocyte-derived DCs and freshly isolated peripheral blood myeloid DCs from lupus patients displayed an abnormal phenotype characterized by accelerated differentiation, maturation, and secretion of proinflammatory cytokines. These abnormalities were characterized by higher expression of the DC differentiation marker CD1a, the maturation markers CD86, CD80, and HLA-DR, and the proinflammatory cytokine IL-8. In addition, SLE patients displayed selective down-regulation of the maturation marker CD83 and had abnormal responses to maturation stimuli. These abnormalities have functional relevance, as SLE DCs were able to significantly increase proliferation and activation of allogeneic T cells when compared with control DCs. We conclude that myeloid DCs from SLE patients display significant changes in phenotype which promote aberrant T cell function and could contribute to the pathogenesis of SLE and organ damage.

Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

“…Koller et al [14] reported comparable expression of CD86 and even lower expression of MHC class II. However, recent data obtained by Ding et al [17] and Decker et al [16] was more comparable to our findings. Different results in the more recent studies may have occurred due to younger DC populations (days 5-7 versus day 8 in the Koller et al study [14]), or maturation effects from the use of fetal bovine serum (FBS) to generate cells [26].…”

“…It was suggested that patients with SLE have increased differentiation of precursor cells into monocyte-derived DC due to the effect of IFN-a produced by pDC [13]. Myeloid DC were found to be either spontaneously hypo- [14,15] or hyperactivated [16,17] with a decreased [14,15] or increased [17] mixed lymphocyte reaction (MLR). However, their capacity and function following apoptotic cell interaction was not examined.…”

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

“…In this sense, emergent data suggest that DCs heterogeneity and activation states may be involved in autoimmune response either by a dysregulation of DC maturation towards their chronic activation and their cytokine secretion or by defective induction and maintenance of antigen-specific peripheral T-cell tolerance. Thus, abnormalities reported in SLE patients may represent DC-intrinsic defects and/or result of secondary defects such an imbalance of cytokine signals that could generate directly prime of autoreactive T cells, or fail to prime regulatory T-cell subsets, or even shift a Th1/Th2 balance to an unfavourable outcome [19][20][21][22][23].…”

Customising an antibody leukocyte capture microarray for systemic lupus erythematosus: Beyond biomarker discovery

“…DCs produce IFN-a in response to a variety of stimuli including antigen-(auto)antibody complexes, viruses, stimulation of the Toll-like receptors (TLRs) and other stimuli [21] that lead to stimulation of cells of the innate and adaptive immune system. In the past few years, significant progress has been made in elucidating the important role that IFN-aproducing plasmacytoid DCs have in promoting autoimmune responses in SLE [22][23][24][25]. TLR can recognise a range of host components released by damaged or dying cells, e.g.…”