Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes
Plasma levels of HDL cholesterol are inversely associated with CVD progression. It is becoming increasingly clear that HDL plays important roles in immunity that go beyond its traditionally understood roles in lipid transport. We previously reported that HDL interaction with regulatory T cells (Treg...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227523000986 |
| _version_ | 1797676685541244928 |
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| author | Laura Atehortua Jamie Morris Scott E. Street Nicholas Bedel W. Sean Davidson Claire A. Chougnet |
| author_facet | Laura Atehortua Jamie Morris Scott E. Street Nicholas Bedel W. Sean Davidson Claire A. Chougnet |
| author_sort | Laura Atehortua |
| collection | DOAJ |
| description | Plasma levels of HDL cholesterol are inversely associated with CVD progression. It is becoming increasingly clear that HDL plays important roles in immunity that go beyond its traditionally understood roles in lipid transport. We previously reported that HDL interaction with regulatory T cells (Treg) protected them from apoptosis, which could be a mechanism underlying the broad anti-inflammatory effect of HDL. Herein, we extend our work to show that HDL interacts mainly with memory Treg, particularly with the highly suppressive effector memory Treg, by limiting caspase-dependent apoptosis in an Akt-dependent manner. Reconstitution experiments identified the protein component of HDL as the primary driver of the effect, though the most abundant HDL protein, apolipoprotein A-I (APOA1), was inactive. In contrast, APOE-depleted HDL failed to rescue effector memory Treg, suggesting the critical role of APOE proteins. HDL particles reconstituted with APOE, and synthetic phospholipids blunted Treg apoptosis at physiological concentrations. The APOE3 and APOE4 isoforms were the most efficient. Similar results were obtained when lipid-free recombinant APOEs were tested. Binding experiments showed that lipid-free APOE3 bound to memory Treg but not to naive Treg. Overall, our results show that APOE interaction with Treg results in blunted caspase-dependent apoptosis and increased survival. As dysregulation of HDL-APOE levels has been reported in CVD and obesity, our data bring new insight on how this defect may contribute to these diseases. |
| first_indexed | 2024-03-11T22:32:57Z |
| format | Article |
| id | doaj.art-7154b2275503415faba88b6eff8b3219 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-03-11T22:32:57Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7154b2275503415faba88b6eff8b32192023-09-23T05:09:47ZengElsevierJournal of Lipid Research0022-22752023-09-01649100425Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytesLaura Atehortua0Jamie Morris1Scott E. Street2Nicholas Bedel3W. Sean Davidson4Claire A. Chougnet5Division of Immunobiology, Cincinnati Children’s Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USADivision of Experimental Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USADivision of Experimental Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USADivision of Experimental Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USADivision of Experimental Pathology, Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USADivision of Immunobiology, Cincinnati Children’s Hospital Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA; For correspondence: Claire A. ChougnetPlasma levels of HDL cholesterol are inversely associated with CVD progression. It is becoming increasingly clear that HDL plays important roles in immunity that go beyond its traditionally understood roles in lipid transport. We previously reported that HDL interaction with regulatory T cells (Treg) protected them from apoptosis, which could be a mechanism underlying the broad anti-inflammatory effect of HDL. Herein, we extend our work to show that HDL interacts mainly with memory Treg, particularly with the highly suppressive effector memory Treg, by limiting caspase-dependent apoptosis in an Akt-dependent manner. Reconstitution experiments identified the protein component of HDL as the primary driver of the effect, though the most abundant HDL protein, apolipoprotein A-I (APOA1), was inactive. In contrast, APOE-depleted HDL failed to rescue effector memory Treg, suggesting the critical role of APOE proteins. HDL particles reconstituted with APOE, and synthetic phospholipids blunted Treg apoptosis at physiological concentrations. The APOE3 and APOE4 isoforms were the most efficient. Similar results were obtained when lipid-free recombinant APOEs were tested. Binding experiments showed that lipid-free APOE3 bound to memory Treg but not to naive Treg. Overall, our results show that APOE interaction with Treg results in blunted caspase-dependent apoptosis and increased survival. As dysregulation of HDL-APOE levels has been reported in CVD and obesity, our data bring new insight on how this defect may contribute to these diseases.http://www.sciencedirect.com/science/article/pii/S0022227523000986HDLAPOEmemory TregapolipoproteinsapoptosisCVD |
| spellingShingle | Laura Atehortua Jamie Morris Scott E. Street Nicholas Bedel W. Sean Davidson Claire A. Chougnet Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes Journal of Lipid Research HDL APOE memory Treg apolipoproteins apoptosis CVD |
| title | Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes |
| title_full | Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes |
| title_fullStr | Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes |
| title_full_unstemmed | Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes |
| title_short | Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes |
| title_sort | apolipoprotein e containing hdl decreases caspase dependent apoptosis of memory regulatory t lymphocytes |
| topic | HDL APOE memory Treg apolipoproteins apoptosis CVD |
| url | http://www.sciencedirect.com/science/article/pii/S0022227523000986 |
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