High-density lipoprotein phospholipids interfere with dendritic cell Th1 functional maturation

Perrin-Cocon, Laure; Diaz, Olivier; Carreras, Marı́a Cecilia; Dollet, Sandra; Guironnet‐Paquet, Aurélie; André, Patrice; Lotteau, Vincent

doi:10.1016/j.imbio.2011.07.030

Cited by 30 publications

(22 citation statements)

References 57 publications

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“…To this end, treatment of BMDCs with rHDL resulted in reduced expression of MHC-II and co-stimulatory molecules that are required for efficient antigen-presentation and activation of T lymphocytes. This is in line with previous reports revealing a role of HDL and apoA-I on human DC differentiation and function (41, 42). Antigen loading to MHC-II is mediated either through the classical or via the autophagy pathway (43, 44).…”

Section: Discussionsupporting

confidence: 93%

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

Tiniakou

Δράκος

Sinatkas

et al. 2015

The Journal of Immunology

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Aberrant levels and function of the potent anti-inflammatory high-density lipoprotein (HDL) and accelerated atherosclerosis have been reported in patients with autoimmune inflammatory diseases. Whether HDL affects the development of an autoimmune response remains elusive. Herein, we utilized apolipoprotein A-I deficient (apoA-I-/-) mice, characterized by diminished circulating HDL levels, to delineate the role of HDL in autoimmunity. ApoA-I-/-mice exhibited increased severity of antigen-induced arthritis compared to wild-type mice and this was associated with elevated Th1 and Th17 cell reactivity in the draining lymph nodes (dLNs). Furthermore, reconstituted HDL (rHDL) attenuated IFN-γ and IL-17 secretion by antigen-specific T cells upon stimulation of dLNs in vitro. The suppressive effects of rHDL were mediated through modulation of dendritic cell (DC) function. Specifically, rHDL-treated DCs demonstrated an immature phenotype characterized by downregulated co-stimulatory molecules, the release of low amounts of pro-inflammatory cytokines, and failure to promote T cell proliferation in vitro. The mechanism of action involved the inhibition of NF-κB nuclear translocation and the decrease of Myd88 mRNA levels by rHDL. Finally, modulation of DC function by rHDL was critically dependent on the presence of SR-BIand ABCA1 but not of the ABCG1 transporter. These findings reveal a novel role of HDL in the regulation of adaptive inflammatory responses through suppression of DC function that could be exploited therapeutically in autoimmune inflammatory diseases.

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Section: Discussionsupporting

confidence: 93%

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

Tiniakou

Δράκος

Sinatkas

et al. 2015

The Journal of Immunology

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“…In addition, HDL's influence on apoA-1, component lipids, and key enzymes (PON1) can modulate endothelial functions and exert anti-oxidant and antiinflammatory effects (Khera et al 2011). It is also clear that by modulating cellular cholesterol levels, HDL plays an important modulatory role in innate and cellular immunity (Perrin-Cocon et al 2012;Wang et al 2012). Emerging evidence suggests that the anti-inflammatory and modulatory effects of HDL may in fact extend beyond their capacity to mediate cholesterol efflux to involve additional mechanisms (Norata et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

Larbi

Fortin

Dupuis

et al. 2014

AGE

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Natural aging is accompanied by a dysregulation of the host immune response that has well-known clinical consequences but poorly defined underlying causes. It has previously been reported that advancing age is associated with an increase in membrane cholesterol level in T cells. The aim of this study was to investigate whether high-density lipoprotein (HDL) can modulate the age-related accumulation of membrane cholesterol in T cells and impact on their subsequent responsiveness. Our data reveal that cholesterol metabolism, influx, and efflux are altered in T cells with aging, which may in part explain the increase in membrane cholesterol level observed in T cells in elderly individuals. HDL was unable to promote reverse cholesterol transport in T cells from elderly subjects with the same efficiency as was observed in T cells from young subjects besides unchanged ABCA-1 and SR-BI expressions. HDL exhibited a short-acting co-stimulatory effect by enhancing T cell production of interleukin-2 (IL-2). Moreover, HDL from healthy normolipemic individuals exerted differential effects on T cell proliferation that depended on the age of the HDL donor. Finally, HDL modulated TCR/CD28 activation by inducing sustained signaling through pLck, pERK, and pAkt. These data suggest that HDL has immunomodulatory effects on T cells that are influenced by age.

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“…By contrast, patients with isolated arterial hypertension present with reduced content of total HDL phospholipid and proinfl ammatory signaling via the nuclear factor kappa B (NFkB) pathway and may thereby contribute to the capacity of HDL to inhibit infl ammation in endothelial cells ( 63,64 ). In addition, 1-palmitoyl-2-linoleyl PC can account for the ability of HDL to inhibit the activation of T cells mediated by dendritic cells ( 65 ).…”

Section: Phospholipidsmentioning

confidence: 99%

Unraveling the complexities of the HDL lipidome

Kontush

Lhomme

Chapman

2013

Journal of Lipid Research

309

247

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This article is available online at http://www.jlr.org For many years, HDL lipids were predominantly characterized in terms of the content of their major classes, notably phospholipids, unesterifi ed (free) sterols (predominantly cholesterol), cholesteryl esters, and triglycerides. Cholesterol is the most characteristic component of the HDL lipidome as, in the form of HDL-cholesterol, it represents a major independent negative risk factor for cardiovascular disease (see other reviews in this Thematic Series). It is not cholesterol, however, but phospholipids that quantitatively predominate in the HDL lipidome, accounting, together with sphingomyelin (SM), for 40-60 wt% of total lipid, with lesser proportions of cholesteryl esters (30-40%), triglycerides (5-12%), and free cholesterol (5-10%). Structurally, individual HDL lipid classes fulfi ll distinct functions; phospholipids constitute the surface lipid monolayer of HDL, whereas cholesteryl esters and triglycerides form the hydrophobic lipid core. Unesterifi ed sterols are predominantly located to the surface monolayer, partially penetrating the core.Recent technological advances in mass spectrometry (MS) have enabled application of this powerful technique to provide a detailed identifi cation and quantifi cation of individual molecular species of lipids in the framework of the fi eld known as lipidomics. Application of this approach to plasma lipoproteins has revealed complex profi les consisting of hundreds of molecular lipid species that have been quantifi ed in major lipoprotein classes, including HDL (reviewed in Refs. 1-3 High density lipoproteins (HDL) are small, dense, protein-rich particles compared with other plasma lipoprotein classes. Despite the elevated abundance of multiple structural and functional proteins in HDL particles (see other reviews in this Thematic Series), roughly half of total HDL mass is accounted for by lipid components.

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High-density lipoprotein phospholipids interfere with dendritic cell Th1 functional maturation

Cited by 30 publications

References 57 publications

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

Immunomodulatory role of high-density lipoproteins: impact on immunosenescence

Unraveling the complexities of the HDL lipidome

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