CD8+ T Cells in Atherosclerosis

Schäfer, Sarah; Zernecke, Alma

doi:10.3390/cells10010037

Cited by 65 publications

(40 citation statements)

References 94 publications

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“…The control of lipid metabolism is central to the appropriate differentiation and functions of T lymphocytes ( Howie et al, 2017 ), and it was according to our result that T cell pathways mainly enriched in adipose tissue of OSA. In early atherosclerosis, CD8 T cells control monopoiesis and macrophage accumulation and contribute to macrophage cell death in atherosclerotic plaques ( Schäfer and Zernecke, 2020 ). While in our study, CD8 T cells were positively correlated with Macrophages M0, Macrophages M2, and negatively correlated with monocytes.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Prognostic Factors of Lipid Metabolism in Obstructive Sleep Apnea

Wang

Dai

2021

Front. Genet.

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Background: Obstructive sleep apnea (OSA) is considered to be an independent factor affecting lipid metabolism. This study explored the relationship between immune genes and lipid metabolism in OSA.Methods: Immune-related Differentially Expressed Genes (DEGs) were identified by analyzing microarray data sets from the Gene Expression Omnibus (GEO) database. Subsequently, we conducted protein-protein interaction (PPI) network analysis and calculated their Gene Ontology (GO) semantic similarity. The GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Disease Ontology (DO), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were employed for functional enrichment analyses and to determine the most significant functional terms. Combined with the results of boruta and random forest, we selected predictors to build a prognostic model, along with seeking out the potential TFs and target drugs for the predictive genes.Results: Immune-related DEGs included 64 genes upregulated and 98 genes downregulated. The enrichment analysis might closely associate with cell adhesion and T cell-mediated immunity pathways and there were many DEGs involved in lipid and atherosclerosis signaling pathways. The highest-ranking hub gene in PPI network have been reported lowly expressed in OSA. In line with the enrichment analysis, DO analysis reveal that respiratory diseases may be associated with OSA besides immune system disorders. Consistent with the result of the KEGG pathway, the analysis of GSVA revealed that the pro-inflammation pathways are associated with OSA. Monocytes and CD8 T cells were the predominant immune cells in adipose tissue. We built a prognostic model with the top six genes, and the prognostic genes were involved in the polarization of macrophage and differentiation of T lymphocyte subsets. In vivo experimental verification revealed that EPGN, LGR5, NCK1 and VIP were significantly down-regulated while PGRMC2 was significantly up-regulated in mouse model of OSA.Conclusions: Our study demonstrated strong associations between immune genes and the development of dyslipidemia in OSA. This work promoted the molecular mechanisms and potential targets for the regulation of lipid metabolism in OSA.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of Prognostic Factors of Lipid Metabolism in Obstructive Sleep Apnea

Wang

Dai

2021

Front. Genet.

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“…The balance between pro-inflammatory effector T-cells (T eff ) and anti-inflammatory regulatory T-cells (T reg ) determines the fate of the plaque ( 98 , 99 ). Briefly, T-helper 1 (T H 1) cells are proatherogenic ( 1 , 100 , 101 ) and dominate mouse and human plaques ( 52 ).…”

Section: Immune Cells Crucially Drive Atherosclerosismentioning

confidence: 99%

Immune Mechanisms of Plaque Instability

Gerhardt

Haghikia

Stapmanns

et al. 2022

Front. Cardiovasc. Med.

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Inflammation crucially drives atherosclerosis from disease initiation to the emergence of clinical complications. Targeting pivotal inflammatory pathways without compromising the host defense could compliment therapy with lipid-lowering agents, anti-hypertensive treatment, and lifestyle interventions to address the substantial residual cardiovascular risk that remains beyond classical risk factor control. Detailed understanding of the intricate immune mechanisms that propel plaque instability and disruption is indispensable for the development of novel therapeutic concepts. In this review, we provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis. From a more global perspective, the article discusses how systemic crises such as acute mental stress or infection abruptly raise plaque vulnerability and summarizes recent advances in understanding the increased cardiovascular risk associated with COVID-19 disease. Stepping outside the box, we highlight the role of gut dysbiosis in atherosclerosis progression and plaque vulnerability. The emerging differential role of the immune system in plaque rupture and plaque erosion as well as the limitations of animal models in studying plaque disruption are reviewed.

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“…T cells within the plaques were activated ( 36 ) and in vitro work showed lesional CD4 + T cells responding to oxidized low-density lipoprotein (oxLDL), which established the theory of T cells contributing to plaque formation ( 37 ). By now, CD4 + and CD8 + T cell responses against plaque-associated autoantigens have been identified to modulate atherogenesis ( 34 , 38 , 39 ). Whereas, T cell reactivity against LDL was originally thought to be induced by oxidation-dependent generation of neoepitopes representing “altered self” ( 37 ), more recent work has identified CD4 + T cells responding to peptides of native Apolipoprotein B (ApoB), the core protein of LDL, chylomicrons, and other lipoprotein particles.…”

Section: Inflammation and Adaptive Immunity In Atherogenesismentioning

confidence: 99%

Immunotherapeutic Strategies in Cancer and Atherosclerosis—Two Sides of the Same Coin

Nettersheim

Picard

Hoyer

et al. 2022

Front. Cardiovasc. Med.

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The development and clinical approval of immunotherapies has revolutionized cancer therapy. Although the role of adaptive immunity in atherogenesis is now well-established and several immunomodulatory strategies have proven beneficial in preclinical studies, anti-atherosclerotic immunotherapies available for clinical application are not available. Considering that adaptive immune responses are critically involved in both carcinogenesis and atherogenesis, immunotherapeutic approaches for the treatment of cancer and atherosclerosis may exert undesirable but also desirable side effects on the other condition, respectively. For example, the high antineoplastic efficacy of immune checkpoint inhibitors, which enhance effector immune responses against tumor cells by blocking co-inhibitory molecules, was recently shown to be constrained by substantial proatherogenic properties. In this review, we outline the specific role of immune responses in the development of cancer and atherosclerosis. Furthermore, we delineate how current cancer immunotherapies affect atherogenesis and discuss whether anti-atherosclerotic immunotherapies may similarly have an impact on carcinogenesis.

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CD8+ T Cells in Atherosclerosis

Cited by 65 publications

References 94 publications

Identification and Validation of Prognostic Factors of Lipid Metabolism in Obstructive Sleep Apnea

Identification and Validation of Prognostic Factors of Lipid Metabolism in Obstructive Sleep Apnea

Immune Mechanisms of Plaque Instability

Immunotherapeutic Strategies in Cancer and Atherosclerosis—Two Sides of the Same Coin

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