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Induction of dendritic cell-mediated T-cell activation by modified but not native low-density lipoprotein in humans and inhibition by annexin a5: involvement of heat shock proteins
- Source :
- Arteriosclerosis, Thrombosis, and Vascular Biology, Arteriosclerosis, Thrombosis, and Vascular Biology, 2015, 35 (1), pp.197-205. ⟨10.1161/ATVBAHA.114.304342⟩
- Publication Year :
- 2014
-
Abstract
- Objective— Atherosclerosis is an inflammatory disease, where activated immunocompetent cells, including dendritic cells (DCs) and T cells are abundant in plaques. Low-density lipoprotein modified either by oxidation (oxLDL) or by human group X-secreted phospholipase A2 (LDLx) and heat shock proteins (HSP), especially HSP60 and 90, have been implicated in atherosclerosis. We previously reported that Annexin A5 inhibits inflammatory effects of phospholipids, decreases vascular inflammation and improves vascular function in apolipoprotein E −/− mice. Here, we focus on the LDLx effects on human DCs and T cells. Approach and Results— Human DCs were differentiated from peripheral blood monocytes, stimulated by oxLDL or LDLx. Naive autologous T cells were cocultured with pretreated DCs. oxLDL and LDLx, in contrast to LDL, induced DC-activation and T-cell proliferation. T cells exposed to LDLx-treated DCs produced interferon-γ, interleukin (IL)-17 but not IL-4 and IL-10. Annexin A5 abrogated LDLx effects on DCs and T cells and increased production of transforming growth factor-β and IL-10. Furthermore, IL-10 producing T cells suppressed primary T-cell activation via soluble IL-10, transforming growth factor-β, and cell–cell contact. Lentiviral-mediated shRNA knock-down HSP60 and 90 in DCs attenuated the effect of LDLx on DCs and subsequent T-cell proliferation. Experiments on DC and T cells derived from carotid atherosclerotic plaques gave similar results. Conclusions— Our data show that modified forms of LDL such as LDLx but not native LDL activate human T cells through DCs. HSP60 and 90 contribute to such T-cell activation. Annexin A5 promotes induction of regulatory T cells and is potentially interesting as a therapeutic agent.
- Subjects :
- MESH: Signal Transduction
Carotid Artery Diseases
MESH: Lipoproteins, LDL
MESH: Annexin A5
MESH: Group X Phospholipases A2
[SDV]Life Sciences [q-bio]
MESH: T-Lymphocyte Subsets
Cell Communication
Lymphocyte Activation
chemistry.chemical_compound
T-Lymphocyte Subsets
Annexin A5
Cells, Cultured
MESH: Cytokines
MESH: Dendritic Cells
Interleukin
MESH: Mitochondrial Proteins
Cell Differentiation
Plaque, Atherosclerotic
Cell biology
[SDV] Life Sciences [q-bio]
Lipoproteins, LDL
medicine.anatomical_structure
Low-density lipoprotein
LDL cholesterol
[SDV.IMM]Life Sciences [q-bio]/Immunology
Cytokines
HSP60
RNA Interference
Inflammation Mediators
Cardiology and Cardiovascular Medicine
MESH: Cells, Cultured
Signal Transduction
MESH: Cell Differentiation
[SDV.IMM] Life Sciences [q-bio]/Immunology
T cell
MESH: RNA Interference
MESH: Inflammation Mediators
T cells
Biology
Transfection
MESH: Coculture Techniques
Mitochondrial Proteins
Heat shock protein
MESH: Cell Proliferation
MESH: Cell Communication
medicine
MESH: HSP90 Heat-Shock Proteins
Group X Phospholipases A2
Humans
MESH: Plaque, Atherosclerotic
HSP90 Heat-Shock Proteins
MESH: Lymphocyte Activation
Cell Proliferation
MESH: Humans
MESH: Carotid Artery Diseases
MESH: Transfection
Dendritic cell
Chaperonin 60
Dendritic Cells
Coculture Techniques
chemistry
Immunology
heat shock proteins
MESH: Chaperonin 60
atherosclerosis
Lipoprotein
Subjects
Details
- ISSN :
- 15244636 and 10795642
- Volume :
- 35
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Accession number :
- edsair.doi.dedup.....b37b603bf083de9b6b4de1f3df659903