title: Lysophosphatidic acid modulates the activation of human monocyte-derived dendritic cells.
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.
authors.affiliation: Division of Pulmonary & Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21212, USA.
authors.forename: Rongbing
authors.initials: R
authors.lastname: Chen
authors.forename: Jessica
authors.initials: J
authors.lastname: Roman
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Erin
authors.initials: E
authors.lastname: West
authors.forename: John
authors.initials: J
authors.lastname: McDyer
authors.forename: Marc A
authors.initials: MA
authors.lastname: Williams
authors.forename: Steve N
authors.initials: SN
authors.lastname: Georas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018920:Coculture Techniques; D017124:Conserved Sequence; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D049368:Receptors, Lysophosphatidic Acid / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D016753:Interleukin-10; C032881:lysophosphatidic acid