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Published on: May 31, 2018
Human dendritic cell responses to lipopolysaccharide and CD40 ligation are differentially regulated by interleukin-10
C Buelens1, V Verhasselt, D De Groote
1Department of Immunology, Hôpital Erasme, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Insights
Interleukin-10 (IL-10) differentially affects dendritic cell (DC) maturation. IL-10 inhibits lipopolysaccharide (LPS)-induced maturation markers and cytokines but not CD40-induced maturation, except for IL-12 production.
Area of Science:
- Immunology
- Cell Biology
Background:
- Dendritic cells (DCs) are crucial for initiating immune responses.
- DC maturation is a complex process involving surface marker expression and cytokine production.
- Interleukin-10 (IL-10) is a key immunomodulatory cytokine.
Purpose of the Study:
- To investigate the differential effects of IL-10 on human DC maturation induced by distinct stimuli.
- To compare IL-10's impact on lipopolysaccharide (LPS)-induced versus CD40 ligand-induced DC maturation pathways.
Main Methods:
- Human DCs were generated from peripheral blood mononuclear cells.
- DCs were matured using either LPS or CD40 ligand stimulation in the presence or absence of IL-10.
- Maturation was assessed by measuring surface marker expression (CD83, CD86) and cytokine production (IL-8, TNF-α, IL-12).
Main Results:
- IL-10 inhibited LPS-induced CD83 and CD86 expression on DCs.
- IL-10 suppressed LPS-induced IL-8 and TNF-α production.
- IL-10 inhibited IL-12 production irrespective of the maturation stimulus (LPS or CD40).
- IL-10 did not inhibit CD40-induced CD83 and CD86 expression.
Conclusions:
- IL-10 differentially regulates LPS-dependent and CD40-dependent DC maturation pathways.
- The findings highlight distinct mechanisms controlling DC maturation based on the activating signal.
- IL-10's selective inhibition provides insights into immune response modulation.
Abstract:
We evaluated the effects of interleukin (IL)-10 on the maturation of human dendritic cells (DC) induced either by lipopolysaccharide (LPS) or CD40 engagement. For this purpose, DC generated by culturing plastic-adherent peripheral blood mononuclear cells for 7 days with granulocyte/macrophage-colony-stimulating factor and IL-4 were incubated for 3 days with either LPS (10 ng/ml) or 3T6 fibroblasts transfected with the gene encoding CD40 ligand, in absence or presence of IL-10. First we found that the membrane expression of CD83, a marker of mature DC, was inhibited by IL-10 when induced by LPS but not by CD40 engagement. Likewise, IL-10 inhibited LPS-induced but not CD40-dependent CD86 (B7.2) up-regulation on DC. Furthermore, IL-10 inhibited the production of IL-8 and tumor necrosis factor-alpha by DC when activated by LPS but not by CD40. In contrast, IL-10 inhibited IL-12 production in both activation systems. We conclude that IL-10 differentially influences LPS-dependent and CD40-dependent pathways of DC maturation.
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