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Published on: October 18, 2016
Lysophosphatidic acid modulates the activation of human monocyte-derived dendritic cells
Rongbing Chen1, Jessica Roman, Jia Guo
1Division of Pulmonary & Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21212, USA.
Insights
Lysophosphatidic acid (LPA) modifies lipopolysaccharide (LPS)-induced dendritic cell (DC) maturation, enhancing T cell interferon-gamma production. LPA fine-tunes DC responses but does not dominate T helper cell polarization.
Area of Science:
- Immunology
- Cell Biology
Background:
- Lysophosphatidic acid (LPA) is a bioactive lipid involved in immune regulation.
- The precise impact of LPA on dendritic cell (DC) function and subsequent T cell polarization remains incompletely understood.
Purpose of the Study:
- To investigate how LPA influences the maturation of human monocyte-derived DCs.
- To determine the effect of LPA-matured DCs on T cell activation and polarization.
Main Methods:
- Human monocyte-derived DCs were differentiated and matured with IL-4, GM-CSF, LPA, and LPS.
- DC activation markers (co-stimulatory receptors, cytokines) were analyzed.
- DC:T cell co-culture models assessed T cell activation and polarization (IFN-gamma, IL-4 secretion).
Main Results:
- LPS induced dose-dependent DC maturation, increasing CD86, IL-6, and IL-10.
- LPA attenuated LPS-induced IL-6 production but did not alter IL-10 or T cell proliferation.
- LPA- and LPS-matured DCs enhanced interferon-gamma (IFN-gamma) production in co-cultured T cells.
Conclusions:
- LPA modulates LPS-driven human myeloid DC maturation.
- LPA-primed DCs promote enhanced IFN-gamma and IL-4 secretion in allogeneic T cells.
- LPA fine-tunes DC immunomodulatory capacity without overriding their influence on Th cell polarization.
Abstract:
Lysophosphatidic acid (LPA) is a biologically active lysophospholipid that can regulate immune activation. LPA can activate T cells and dendritic cells (DCs), but the effects of LPA on the ability of DCs to influence T cell polarization are not well understood. Human monocyte-derived DCs were differentiated in vitro in the presence of interleukin-4 (IL-4) and granulocyte-macrophage colonystimulating factor (GM-CSF), and matured with LPA and lipopolysaccharide (LPS) alone or in combination. DC activation was monitored by analyzing cell-surface expression of co-stimulatory receptors and cytokine production. The ability of DCs to influence T cell activation was determined using two models of DC:T cell co-culture. Maturation with LPS induced dose-dependent DC activation characterized by enhanced expression of co-stimulatory molecules (e.g., CD86) and production of cytokines including IL-6 and IL-10. Co-incubation with LPA attenuated the LPS-induced production of IL-6, without significantly affecting IL-10 secretion or the ability of DC to promote T cell proliferation. DCs matured in the presence of both LPA and LPS enhanced the production of interferon-gamma (IFN-gamma) when co-cultured with allogeneic T cells, compared with DC matured by LPS alone. Similar results were found using a model of allogeneic naïve T cell differentiation, where LPA- plus LPS-matured DC enhanced IFN-gamma as well as IL-4 secretion after restimulation. Lysophosphatidic acid fine-tunes the effects of LPS on human myeloid DC maturation, but does not exert a dominant effect on the ability of DC to influence Th cell polarization.
