title: Serum lipids regulate dendritic cell CD1 expression and function.
abstract: Dendritic cells (DCs) are highly potent antigen-presenting cells (APCs) and play a vital role in stimulating naïve T cells. Treatment of human blood monocytes with the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 stimulates them to develop into immature dendritic cells (iDCs) in vitro. DCs generated by this pathway have a high capacity to prime and activate resting T cells and prominently express CD1 antigen-presenting molecules on the cell surface. The presence of human serum during the differentiation of iDCs from monocytes inhibits the expression of CD1a, CD1b and CD1c, but not CD1d. Correspondingly, T cells that are restricted by CD1c showed poor responses to DCs that were generated in the presence of human serum, while the responses of CD1d-restricted T cells were enhanced. We chemically fractionated human serum to isolate the bioactive factors that modulate surface expression of CD1 proteins during monocyte to DC differentiation. The human serum components that affected CD1 expression partitioned with polar organic soluble fractions. Lysophosphatidic acid and cardiolipin were identified as lipids present in normal human serum that potently modulate CD1 expression. Control of CD1 expression was mediated at the level of gene transcription and correlated with activation of the peroxisome proliferator-activated receptor (PPAR) nuclear hormone receptors. These findings indicate that the ability of human DCs to present lipid antigens to T cells through expression of CD1 molecules is sensitively regulated by lysophosphatidic acid and cardiolipin in serum, which are ligands that can activate PPAR transcription factors.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Leslie
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dascher
authors.forename: Katherine
authors.initials: K
authors.lastname: Cembrola
authors.forename: Maria A
authors.initials: MA
authors.lastname: Townes
authors.forename: David L
authors.initials: DL
authors.lastname: Hava
authors.forename: Lynne C
authors.initials: LC
authors.lastname: Hugendubler
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mueller
authors.forename: Lisa
authors.initials: L
authors.lastname: Fox
authors.forename: Carme
authors.initials: C
authors.lastname: Roura-Mir
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.forename: Michael S
authors.initials: MS
authors.lastname: Vincent
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gumperz
authors.forename: Petr A
authors.initials: PA
authors.lastname: Illarionov
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Carol G
authors.initials: CG
authors.lastname: Reynolds
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D047492:Peroxisome Proliferator-Activated Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D044967:Serum / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D018949:Antigens, CD1; D008055:Lipids; D047492:Peroxisome Proliferator-Activated Receptors