Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes

Atehortua, Laura; Morris, Jamie; Street, Scott E.; Bedel, Nicholas; Davidson, W. Sean; Chougnet, Claire A.

doi:10.1016/j.jlr.2023.100425

Cited by 3 publications

(5 citation statements)

References 53 publications

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“…HDL-APOE3 and APOE4 were antiapoptotic for memory Treg cells at physiological levels, decreasing the activation of caspase-3/7, while APOE2 did not protect Treg cells from apoptosis. 103 Our study did not indicate an effect of the HDL sphingolipids in Treg survival. In contrast, others have reported that S1PR1 deficiency, which recognizes S1P in the HDL, made Treg cells more susceptible to apoptosis.…”

Section: Apoptosiscontrasting

confidence: 62%

“…Our data suggest that HDLs bind predominantly to Treg cells, particularly the effector memory Treg cells, and not to other CD4+ T-cell subsets. However, although HDL interactions upregulate lipid metabolism and oxidative phosphorylation in Treg cells, and blunted apoptosis, 112 our recent data showing that the protein component and not the lipid from the HDL mediates this effect, 103 suggest that HDL acts more by signaling downstream metabolic pathways than through passive uptake.…”

Section: Immunomodulatory Properties Of Hdl In Cd4+ T Cellsmentioning

confidence: 87%

“…We uncovered a novel connection between HDL and CD4+ T cells that regulates apoptosis. 103,112 In vitro, HDL directly bound and promoted the survival of human Treg cells but not that of naive or memory conventional CD4+ T cells 112 (Figure 3). Furthermore, Treg cells, specifically the highly suppressive effector memory Treg cells, directly interacted with HDL-APOE and lipid-free APOE.…”

Section: Apoptosismentioning

confidence: 99%

“…102 The increase in Treg frequency observed in these mice may be due to an effect of HDL-APOA1 on Treg differentiation, more than a direct effect on Treg homeostasis, as we have shown a direct effect of APOE, and not APOA1, in how HDL blunt human Treg apoptosis. 103 On the other hand, APOA1 transgenic mice had milder systemic lupus erythematosus glomerulonephritis due to reduced Th1 and Tfh frequency and responses, independently of changes in their Treg pool. 94 Additionally, APOA2 has been proposed to suppress IFNγ production of in vitro stimulated mouse and human CD4+ T cells by inhibiting the ERK (extracellular signal-regulated kinase)-MAPK and NFAT (nuclear factor of activated T cells) signaling pathways.…”

Section: Differentiation and Cytokine Productionmentioning

confidence: 99%

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Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties

Atehortua,

Davidson,

Chougnet

2024

ATVB

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Several studies in animal models and human cohorts have recently suggested that HDLs (high-density lipoproteins) not only modulate innate immune responses but also adaptative immune responses, particularly CD4+ T cells. CD4+ T cells are central effectors and regulators of the adaptive immune system, and any alterations in their homeostasis contribute to the pathogenesis of cardiovascular diseases, autoimmunity, and inflammatory diseases. In this review, we focus on how HDLs and their components affect CD4+ T-cell homeostasis by modulating cholesterol efflux, immune synapsis, proliferation, differentiation, oxidative stress, and apoptosis. While the effects of apoB-containing lipoproteins on T cells have been relatively well established, this review focuses specifically on new connections between HDL and CD4+ T cells. We present a model where HDL may modulate T cells through both direct and indirect mechanisms.

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Section: Apoptosiscontrasting

confidence: 62%

Section: Immunomodulatory Properties Of Hdl In Cd4+ T Cellsmentioning

confidence: 87%

Section: Apoptosismentioning

confidence: 99%

Section: Differentiation and Cytokine Productionmentioning

confidence: 99%

See 2 more Smart Citations

Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties

Atehortua,

Davidson,

Chougnet

2024

ATVB

Self Cite

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“…Lastly, apoE may play a role in the antiinflammatory properties of HDLs. It has been recently found that apoE-containing HDLs promote the survival of the anti-inflammatory regulatory T lymphocytes [95]. Interestingly, apoE-containing HDL-C is inversely associated with coronary artery calcium score and stenosis [96].…”

Section: Overview Of Hdl Anti-inflammatory Functionsmentioning

confidence: 99%

Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes

Denimal

2023

Antioxidants

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(1) Background: high-density lipoproteins (HDLs) exhibit antioxidant and anti-inflammatory properties that play an important role in preventing the development of atherosclerotic lesions and possibly also diabetes. In turn, both type 1 diabetes (T1D) and type 2 diabetes (T2D) are susceptible to having deleterious effects on these HDL functions. The objectives of the present review are to expound upon the antioxidant and anti-inflammatory functions of HDLs in both diabetes in the setting of atherosclerotic cardiovascular diseases and discuss the contributions of these HDL functions to the onset of diabetes. (2) Methods: this narrative review is based on the literature available from the PubMed database. (3) Results: several antioxidant functions of HDLs, such as paraoxonase-1 activity, are compromised in T2D, thereby facilitating the pro-atherogenic effects of oxidized low-density lipoproteins. In addition, HDLs exhibit diminished ability to inhibit pro-inflammatory pathways in the vessels of individuals with T2D. Although the literature is less extensive, recent evidence suggests defective antiatherogenic properties of HDL particles in T1D. Lastly, substantial evidence indicates that HDLs play a role in the onset of diabetes by modulating glucose metabolism. (4) Conclusions and perspectives: impaired HDL antioxidant and anti-inflammatory functions present intriguing targets for mitigating cardiovascular risk in individuals with diabetes. Further investigations are needed to clarify the influence of glycaemic control and nephropathy on HDL functionality in patients with T1D. Furthermore, exploring the effects on HDL functionality of novel antidiabetic drugs used in the management of T2D may provide intriguing insights for future research.

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APOE ε4–associated downregulation of the IL‐7/IL‐7R pathway in effector memory T cells: Implications for Alzheimer's disease

Zhang,

Cheng,

Tang

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONThe apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive.METHODSThe present study enrolled 54 patients diagnosed with late‐onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non‐carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA‐seq) and single‐cell RNA sequencing (scRNA‐seq) analysis of peripheral blood mononuclear cells (PBMCs).RESULTSPlasma tumor necrosis factor α, interferon γ, and interleukin (IL)‐33 levels increased in the APOE ε4 carriers but IL‐7 expression notably decreased. A negative correlation was observed between plasma IL‐7 level and the hippocampal atrophy degree. Additionally, the expression of IL‐7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA‐seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells.DISCUSSIONThese findings shed light on the role of the downregulated IL‐7/IL‐7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy.Highlights The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)‐7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL‐7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL‐7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL‐7/IL‐7R signal pathways enriches T cells.

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Apolipoprotein E-containing HDL decreases caspase-dependent apoptosis of memory regulatory T lymphocytes

Cited by 3 publications

References 53 publications

Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties

Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties

Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes

APOE ε4–associated downregulation of the IL‐7/IL‐7R pathway in effector memory T cells: Implications for Alzheimer's disease

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