Low density lipoprotein promotes human naive T cell differentiation to Th1 cells

Newton, A. H.; Benedict, Stephen H.

doi:10.1016/j.humimm.2014.04.017

Cited by 17 publications

(12 citation statements)

References 38 publications

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“…M2 macrophages have been observed to direct T cell activation and maturation , and so we expected a change from a Th1 to a Th2 response in cultures with CRP, especially since CRP has been reported to suppress Th1 cell differentiation . Others have shown that oxidized lipids induce maturation of naïve T cells to Th1 cells ; thus it is possible that the Th1 response could become chronic or predominant based on continuous recruitment of new cells to a proinflammatory phenotype (Fig. ).…”

Section: Discussionmentioning

confidence: 99%

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Trial

Cieslik

Entman

2016

Immunity, Inflammation and Disease

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IntroductionWe studied monocyte transendothelial migration and subsequent polarization into M1/M2 macrophages in response to C‐reactive protein (CRP) with two disease‐related ligands: (1) phosphocholine (PC) and (2) multilamellar liposomes containing both unoxidized and oxidized forms of the lipid, phosphatidylcholine. These ligands differ in biological origin: PC is present on bacterial cell walls while oxidized lipids are present in atherogenic lipids.MethodsWe used an in vitro model of human monocyte transendothelial migration and assessed the polarization of monocytes and T cells and signaling through Fcγ receptors in monocytes.ResultsCRP without ligands did not promote M2 macrophage differentiation over background levels. However, when paired with either ligand, it increased M2 numbers. M2 differentiation was dependent on IL‐13, and in the case of CRP with PC, was associated with a Th2 response. Paradoxically, while CRP with PC initiated a Th2 response, the combination of liposomes with CRP resulted in a Th1 response without any change in Th2 numbers despite association with M2 macrophage polarization. To resolve the conundrum of an anti‐inflammatory macrophage response coexisting with a proinflammatory T cell response, we investigated signaling of CRP and its ligands through Fcγ receptors, which leads to macrophage activation independent of T cell signaling. We found that CRP plus PC acted via FcγRI, whereas CRP with liposomes bound to FcγRII. Both were activating signals as evidenced by SYK phosphorylation.ConclusionWe conclude that CRP with ligands can promote M2 macrophage differentiation to fibroblasts through FcγR activation, and this may result in an anti‐inflammatory influence despite a proinflammatory T cell environment caused by oxidized lipids. The potential relationship of this mechanism to chronic inflammatory disease is discussed.

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Section: Discussionmentioning

confidence: 99%

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Trial

Cieslik

Entman

2016

Immunity, Inflammation and Disease

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“…CD3 + CD4 + T cell isolation from peripheral blood was conducted through negative selection using a Human CD4 + T cell enrichment kit as directed by the manufacturer (Stemcell Technologies, Vancouver, BC, Canada). Purity was assessed following cell isolation by staining with anti‐CD4‐Alexa Fluor 700 (RPA‐T4) and all samples were >97% CD4 + by flow cytometry (Kohlmeier et al ; Newton and Benedict, ; Siedlik et al ). After purification, the cells were resuspended in warm Immunocult‐XF T cell expansion medium (Stemcell Technologies, Vancouver, BC, Canada).…”

Section: Methodsmentioning

confidence: 99%

CD4⁺T cell activation and associated susceptibility to HIV‐1 infection in vitro increased following acute resistance exercise in human subjects

et al. 2019

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Early studies in exercise immunology suggested acute bouts of exercise had an immunosuppressive effect in human subjects. However, recent data, show acute bouts of combined aerobic and resistance training increase both lymphocyte activation and proliferation. We quantified resistance exercise‐induced changes in the activation state of CD4+ T lymphocytes via surface protein expression and using a medically relevant model of infection (HIV‐1). Using a randomized cross‐over design, 10 untrained subjects completed a control and exercise session. The control session consisted of 30‐min seated rest while the exercise session entailed 3 sets × 10 repetitions of back squat, leg press, and leg extensions at 70% 1‐RM with 2‐min rest between each set. Venous blood samples were obtained pre/post each session. CD4+ T lymphocytes were isolated from whole blood by negative selection. Expression of activation markers (CD69 & CD25) in both nonstimulated and stimulated (costimulation through CD3+CD28) cells were assessed by flow cytometry. Resistance exercised‐induced effects on intracellular activation was further evaluated via in vitro infection with HIV‐1. Nonstimulated CD4+ T lymphocytes obtained postexercise exhibited elevated CD25 expression following 24 h in culture. Enhanced HIV‐1 replication was observed in cells obtained postexercise. Our results demonstrate that an acute bout of resistance exercise increases the activation state of CD4+ T lymphocytes and results in a greater susceptibility to HIV‐1 infection in vitro. These findings offer further evidence that exercise induces activation of T lymphocytes and provides a foundation for the use of medically relevant pathogens as indirect measures of intracellular activation.

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“…Low density lipoprotein(LDL) in the arterial wall is generally oxidized to oxidized LDL (oxLDL), which is atherogenic, and induces vascular endothelial cells to express adhesion molecules, cytokines and chemokines that attract immune cells 5 , 148 - 152 . Amy H. Newton et al 148 found that naïve cells become activated and differentiate to mature effector T cells that are Th1, Th2 or Treg cells. OxLDL and high density lipoprotein (HDL) regulate activation of macrophages and endothelial cells, and T cells, which perpetuate atherogenesis by promoting cell-mediated responses and inflammation.…”

Section: Aging and Atherosclerosismentioning

confidence: 99%

The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response

et al. 2018

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Atherosclerosis is one kind of chronic inflammatory disease, in which multiple types of immune cells or factors are involved. Data from experimental and clinical studies on atherosclerosis have confirmed the key roles of immune cells and inflammation in such process. The thymus as a key organ in T lymphocyte ontogenesis has an important role in optimizing immune system function throughout the life, and dysfunction of thymus has been proved to be associated with severity of atherosclerosis. Based on previous research, we begin with the hypothesis that low density lipoprotein or cholesterol reduces the expression of the thymus transcription factor Foxn1 via low density lipoprotein receptors on the membrane surface and low density lipoprotein receptor related proteins on the cell surface, which cause the thymus function decline or degradation. The imbalance of T cell subgroups and the decrease of naive T cells due to thymus dysfunction cause the increase or decrease in the secretion of various inflammatory factors, which in turn aggravates or inhibits atherosclerosis progression and cardiovascular events. Hence, thymus may be the pivotal role in coronary heart disease mediated by atherosclerosis and cardiovascular events and it can imply a novel treatment strategy for the clinical management of patients with atherosclerosis in addition to different commercial drugs. Modulation of immune system by inducing thymus function may be a therapeutic approach for the prevention of atherosclerosis. Purpose of this review is to summarize and discuss the recent advances about the impact of thymus function on atherosclerosis by the data from animal or human studies and the potential mechanisms.

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Low density lipoprotein promotes human naive T cell differentiation to Th1 cells

Cited by 17 publications

References 38 publications

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

CD4⁺T cell activation and associated susceptibility to HIV‐1 infection in vitro increased following acute resistance exercise in human subjects

The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response

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Low density lipoprotein promotes human naive T cell differentiation to Th1 cells

Cited by 17 publications

References 38 publications

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

Phosphocholine‐containing ligands direct CRP induction of M2 macrophage polarization independent of T cell polarization: Implication for chronic inflammatory states

CD4+T cell activation and associated susceptibility to HIV‐1 infection in vitro increased following acute resistance exercise in human subjects

The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response

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CD4⁺T cell activation and associated susceptibility to HIV‐1 infection in vitro increased following acute resistance exercise in human subjects