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Updated: Jul 14, 2026

Characterization of Human Monocyte-derived Dendritic Cells by Imaging Flow Cytometry: A Comparison between Two Monocyte Isolation Protocols
Published on: October 18, 2016
Immune complexes inhibit differentiation, maturation, and function of human monocyte-derived dendritic cells
Evangelina A Laborde1, Silvia Vanzulli, Macarena Beigier-Bompadre
1Laboratory of Immunology, Institute of Hematologic Research, Academia Nacional de Medicina, Buenos Aires, Argentina.
Insights
Immune complexes (IC) alter dendritic cell (DC) development by interacting with Fc receptors. This impairs T cell response and promotes inflammation, potentially contributing to autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Dendritic Cell Biology
Background:
- Immune complexes (IC) binding to Fc gamma receptors (FcgammaRs) on immune cells initiate critical regulatory and effector responses.
- Dendritic cells (DCs) are key antigen-presenting cells that bridge innate and adaptive immunity.
- Dysfunctional DCs are implicated in the pathogenesis of autoimmune disorders.
Purpose of the Study:
- To investigate the impact of IC on the differentiation, maturation, and function of human monocyte-derived DCs.
- To elucidate the specific Fcgamma receptors involved in mediating IC effects on DCs.
- To understand how IC-induced alterations in DCs may contribute to autoimmune disease development.
Main Methods:
- Human monocytes were differentiated into DCs with or without IC.
- Flow cytometry was used to analyze DC surface marker expression (CD1a, CD14, MHC II, CD68, CD83, CD86, CD40).
- Cytokine production (IL-12, IL-10, CCL22, CXCL8, CCL2) and T cell proliferation assays were performed.
Main Results:
- DCs cultured with IC (IC-DC) exhibited altered differentiation, with lower CD1a and higher CD14 and CD68 expression.
- IC binding primarily involved FcgammaRI and FcgammaRII, leading to immature DC phenotypes with high CD83, CD86, and CD40.
- IC-DC showed reduced IL-12 production, impaired endocytic activity, and decreased T cell proliferation, alongside a proinflammatory cytokine profile.
Conclusions:
- IC significantly disrupt DC differentiation and maturation, skewing them towards a proinflammatory phenotype.
- This IC-induced DC dysfunction, characterized by impaired antigen presentation and T cell activation, mirrors DC states in autoimmune diseases like lupus and arthritis.
- Altered DC maturation by IC may play a crucial role in the pathogenesis of autoimmune diseases.
Abstract:
The interaction between immune complexes (IC) and the receptors for the Fc portion of IgG (FcgammaRs) triggers regulatory and effector functions in the immune system. In this study, we investigated the effects of IC on differentiation, maturation, and functions of human monocyte-derived dendritic cells (DC). When IC were added on day 0, DC generated on day 6 (IC-DC) showed lower levels of CD1a and increased expression of CD14, MHC class II, and the macrophage marker CD68, as compared with normally differentiated DC. The use of specific blocking FcgammaR mAbs indicated that the effect of IC was exerted mainly through their interaction with FcgammaRI and to a lesser extend with FcgammaRII. Immature IC-DC also expressed higher levels of CD83, CD86, and CD40 and the expression of these maturation markers was not further regulated by LPS. The apparent lack of maturation following TLR stimulation was associated with a decreased production of IL-12, normal secretion of IL-10 and CCL22, and increased production of CXCL8 and CCL2. IC-DC displayed low endocytic activity and a reduced ability to induce allogeneic T cell proliferation both at basal and LPS-stimulated conditions. Altogether, these data reveal that IC strongly affect DC differentiation and maturation. Skewing of DC function from Ag presentation to a proinflammatory phenotype by IC resembles the state of activation observed in DC obtained from patients with chronic inflammatory autoimmune disorders, such as systemic lupus erythematosus disease and arthritis. Therefore, the altered maturation of DC induced by IC may be involved in the pathogenesis of autoimmune diseases.
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