title: High density lipoproteins selectively promote the survival of human regulatory T cells.
abstract: HDLs appear to affect regulatory T cell (Treg) homeostasis, as suggested by the increased Treg counts in HDL-treated mice and by the positive correlation between Treg frequency and HDL-cholesterol levels in statin-treated healthy adults. However, the underlying mechanisms remain unclear. Herein, we show that HDLs, not LDLs, significantly decreased the apoptosis of human Tregs in vitro, whereas they did not alter naïve or memory CD4+T cell survival. Similarly, oleic acid bound to serum albumin increased Treg survival. Tregs bound and internalized high amounts of HDL compared with other subsets, which might arise from the higher expression of the scavenger receptor class B type I by Tregs; accordingly, blocking this receptor hindered HDL-mediated Treg survival. Mechanistically, we showed that HDL increased Treg ATP concentration and mitochondrial activity, enhancing basal respiration, maximal respiration, and spare respiratory capacity. Blockade of FA oxidation by etoxomir abolished the HDL-mediated enhanced survival and mitochondrial activity. Our findings thus suggest that Tregs can specifically internalize HDLs from their microenvironment and use them as an energy source. Furthermore, a novel implication of our data is that enhanced Treg survival may contribute to HDLs' anti-inflammatory properties.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Rueda
authors.affiliation: Grupo de Inmunovirología, Facultad de Medicina, Universidad de Antioquia (UdeA), Medellín, Colombia.
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Rodríguez-Perea
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno-Fernandez
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Jackson
authors.affiliation: Division of Experimental Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH.
authors.forename: John T
authors.initials: JT
authors.lastname: Melchior
authors.affiliation: Division of Experimental Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH.
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH. Electronic address: Claire.Chougnet@cchmc.org.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Chougnet
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D018955:CD36 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002470:Cell Survival; D005227:Fatty Acids / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D005227:Fatty Acids; D008075:Lipoproteins, HDL; D000255:Adenosine Triphosphate
keywords: immunology; lipids/oxidation; lymphocytes; mitochondria