title: Conjugated linoleic acid suppresses dendritic cell activation and subsequent Th17 responses.
abstract: PUFAs (polyunsaturated fatty acids) can modify immune responses, so they may have potential therapeutic effects in inflammatory disorders. We previously demonstrated that the cis-9, trans-11 isomer of the PUFA conjugated linoleic acid (CLA) can modulate dendritic cell (DC) cytokine production. Since DCs play a central role in initiating inflammation by directing T helper (Th) cell differentiation, here we examined the effects of CLA on DC maturation and migration and the subsequent generation of Th cell responses. We examined the effect of CLA in vitro on the function of lipopolysaccharide (LPS)-activated bone marrow-derived DCs and ex vivo using cells from mice with high levels of CLA in their diet. We report that CLA inhibits DC migration and modulates TLR-induced production of key cytokines involved in Th cell differentiation both in vitro and in vivo. These changes were accompanied by a significant decrease in expression of MHCII, CD80 and CD86 on the DC surface. Exposure of DCs to CLA suppressed their ability to promote differentiation of naïve T cells into Th1 and/or Th17 cells in vitro and following their adoptive transfer in vivo. Furthermore, in a murine model of endotoxic shock, treatment with CLA suppressed LPS-induced induction of circulating IFN-γ, IL-12p40 and IL-1β. This is the first study to demonstrate that exposure of antigen-presenting cells to CLA can modulate the subsequent Th cell response, and the findings may explain some of the beneficial effects of c9, t11-CLA in inflammatory diseases mediated by Th1 and Th17 cells.
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Eve
authors.initials: E
authors.lastname: Draper
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Joseph
authors.initials: J
authors.lastname: DeCourcey
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Higgins
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: Canavan
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: McEvoy
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Keogh
authors.affiliation: Nutrigenomics Research Group, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Clare
authors.initials: C
authors.lastname: Reynolds
authors.affiliation: Nutrigenomics Research Group, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.affiliation: Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Kingston H G
authors.initials: KH
authors.lastname: Mills
authors.affiliation: Immunomodulation Research Group, School of Biotechnology, Dublin City University, Dublin 9, Ireland. Electronic address: christine.loscher@dcu.ie.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Loscher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D004042:Dietary Fats, Unsaturated; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; D044243:Linoleic Acids, Conjugated; D008070:Lipopolysaccharides; C046938:9,11-linoleic acid; D007371:Interferon-gamma
keywords: Conjugated linoleic acid; Dendritic cell; Th1; Th17