17 results on '"Swart, Maarten"'
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2. Enhancing breadth and durability of humoral immune responses in non-human primates with an adjuvanted group 1 influenza hemagglutinin stem antigen
- Author
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Swart, Maarten, Kuipers, Harmjan, Milder, Fin, Jongeneelen, Mandy, Ritschel, Tina, Tolboom, Jeroen, Muchene, Leacky, van der Lubbe, Joan, Izquierdo Gil, Ana, Veldman, Daniel, Huizingh, Jeroen, Verspuij, Johan, Schmit-Tillemans, Sonja, Blokland, Sven, de Man, Martijn, Roozendaal, Ramon, Fox, Christopher B., Schuitemaker, Hanneke, Capelle, Martinus, Langedijk, Johannes P. M., Zahn, Roland, and Brandenburg, Boerries
- Published
- 2023
- Full Text
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3. Booster vaccination with Ad26.COV2.S or an Omicron-adapted vaccine in pre-immune hamsters protects against Omicron BA.2
- Author
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Swart, Maarten, van der Lubbe, Joan, Schmit-Tillemans, Sonja, van Huizen, Ella, Verspuij, Johan, Gil, Ana Izquierdo, Choi, Ying, Daal, Chenandly, Perkasa, Aditya, de Wilde, Adriaan, Claassen, Erwin, de Jong, Rineke, Wiese, Katrin E., Cornelissen, Lisette, van Es, Marieke, van Heerden, Marjolein, Kourkouta, Eleni, Tahiri, Issam, Mulders, Michel, Vreugdenhil, Jessica, Feddes - de Boer, Karin, Muchene, Leacky, Tolboom, Jeroen, Dekking, Liesbeth, Juraszek, Jarek, Vellinga, Jort, Custers, Jerome, Bos, Rinke, Schuitemaker, Hanneke, Wegmann, Frank, Roozendaal, Ramon, Kuipers, Harmjan, and Zahn, Roland
- Published
- 2023
- Full Text
- View/download PDF
4. The role of extracellular sulfatase-2 in inflammation
- Author
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Swart, Maarten, Troeberg, Linda, Monaco, Claudia, and Williams, Richard
- Subjects
616.7 ,Matrix Biology ,Immunology - Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose molecular pathogenesis serves as a useful model for understanding other chronic inflammatory conditions. Activated macrophages are critical for RA pathogenesis, since they promote the inflammation that causes cartilage damage, bone remodelling, pain and irreversible disability. Macrophages are activated by stimuli in their environment, and responses to these stimuli are fine-tuned by their interactions with highly sulfated heparan sulfate (HS) glycosaminoglycans. HS is sulfated in complex patterns, but 6-O-sulfation of HS glucosamine subunits is known to be particularly important for regulating activity of many cytokines, chemokines and growth factors. 6-O-sulfation is hence tightly regulated, and it is the only HS sulfation motif that can be post-synthetically removed by the extracellular sulfatases SULF1 and SULF2. Although extensively studied in cancer and development, the effect of 6-O-sulfation on inflammation and macrophage function is unknown. In this thesis I showed that Sulf2 is mainly expressed by macrophages, monocytes and dendritic cells. Sulf2 is particularly highly expressed by protective resident alveolar macrophages in the lung and resident synovial macrophages in the joint, indicating that Sulf2 is likely to be important for maintaining homeostasis and suppressing inflammation. Moreover, Sulf2 is downregulated by many inflammatory stimuli, suggesting that downregulation of Sulf2 may enable macrophages to convert from a protective phenotype to an activated inflammatory phenotype. Phagocytosis was increased in Sulf2-deficient macrophages, while macrophage polarisation was inhibited. Sulf2-deficient bone marrow chimeras were generated to investigate the role of Sulf2 in immune function during antigen-induced arthritis (AIA) as an example of a chronic inflammatory disease. These Sulf2-deficient mice developed increased knee swelling, which was associated with an increase in pro-arthritic Th17 cells. In conclusion, SULF2 is important for maintaining homeostasis by suppressing macrophage activation, indicating that therapies reducing 6-O sulfation of HS might be effective for the treatment of RA and other chronic inflammatory diseases.
- Published
- 2020
5. Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis
- Author
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Seneviratne, Anusha N., Edsfeldt, Andreas, Cole, Jennifer E., Kassiteridi, Christina, Swart, Maarten, Park, Inhye, Green, Patricia, Khoyratty, Tariq, Saliba, David, Goddard, Michael E., Sansom, Stephen N., Goncalves, Isabel, Krams, Rob, Udalova, Irina A., and Monaco, Claudia
- Published
- 2017
- Full Text
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6. Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture–prone atherosclerotic plaques.
- Author
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Edsfeldt, Andreas, Swart, Maarten, Singh, Pratibha, Dib, Lea, Sun, Jiangming, Cole, Jennifer E., Park, Inhye, Al-Sharify, Dania, Persson, Ana, Nitulescu, Mihaela, Borges, Patricia Das Neves, Kassiteridi, Christina, Goddard, Michael E., Lee, Regent, Volkov, Petr, Orho-Melander, Marju, Maegdefessel, Lars, Nilsson, Jan, Udalova, Irina, and Goncalves, Isabel
- Subjects
ATHEROSCLEROTIC plaque ,INTERFERONS ,INTERFERON regulatory factors ,MACROPHAGES ,TRANSCRIPTION factors - Abstract
Aims Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. Methods and results Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE
−/− mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE−/− Irf5−/− mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. Conclusion Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Hypercholesterolemia induces a mast cell-CD4+ T-cell interaction in atherosclerosis
- Author
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Pasquale Maffia, Bram Slütter, Swart Maarten, Harm Smeets, Eva Kritikou, Thomas van der Heijden, Ilze Bot, Janine van Duijn, and Johan Kuiper
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medicine.anatomical_structure ,Cd4 t cell ,Chemistry ,Cancer research ,medicine ,Cardiology and Cardiovascular Medicine ,Mast cell - Published
- 2017
8. Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes.
- Author
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Swart, Maarten and Troeberg, Linda
- Subjects
INFLAMMATION ,HEPARAN sulfate proteoglycans ,MACROPHAGES ,BIOSYNTHESIS ,CYTOKINES - Abstract
Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to and regulate the bioactivity more than 400 bioactive protein ligands, including many chemokines, cytokines, and growth factors. This makes them important regulators of the phenotype and behavior of immune cells. Here we review how HS biosynthesis in macrophages is regulated during polarization and in chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma, chronic obstructive pulmonary disease and obesity, by analyzing published micro-array data and mechanistic studies in this area. We describe that macrophage expression of many HS biosynthesis and core proteins is strongly regulated by macrophage polarization, and that these expression patterns are recapitulated in chronic inflammation. Such changes in HS biosynthetic enzyme expression are likely to have a significant impact on the phenotype of macrophages in chronic inflammatory diseases by altering their interactions with chemokines, cytokines, and growth factors. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
9. Combination Approaches with immune-Checkpoint Blockade in Cancer Therapy.
- Author
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Swart, Maarten, Verbrugge, Inge, Beltman, Joost B., Stagg, John, and Corthay, Alexandre
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CANCER treatment ,IMMUNE complexes ,CYTOTOXIC T cells - Abstract
In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-c heckpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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10. New design of an anti-decubitus lying-down support.
- Author
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Swart, Maarten E.
- Published
- 1985
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11. Physico-mechanical aspects of decubitus prevention.
- Author
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Swart, Maarten E.
- Published
- 1985
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12. Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice.
- Author
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Kritikou, Eva, van Puijvelde, Gijs H. M., van der Heijden, Thomas, van Santbrink, Peter J., Swart, Maarten, Schaftenaar, Frank H., Kröner, Mara J., Kuiper, Johan, and Bot, Ilze
- Abstract
Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA
1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425. We show that LPA1/3 inhibition significantly impaired atherosclerosis progression. Treatment with Ki16425 also resulted in reduced CCL2 production and secretion, which led to less monocyte and neutrophil infiltration. Furthermore, we provide evidence that LPA1/3 blockade enhanced the percentage of non-inflammatory, Ly6Clow monocytes and CD4+ CD25+ FoxP3+ T-regulatory cells. Finally, we demonstrate that LPA1/3 antagonism mildly reduced plasma LDL cholesterol levels. Therefore, pharmacological inhibition of LPA1/3 receptors may prove a promising approach to diminish atherosclerosis development. [ABSTRACT FROM AUTHOR]- Published
- 2016
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13. Hypercholesterolemia Induces a Mast Cell-CD4+ T Cell Interaction in Atherosclerosis.
- Author
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Kritikou, Eva, van der Heijden, Thomas, Swart, Maarten, van Duijn, Janine, Slütter, Bram, Kuiper, Johan, Bot, Ilze, Wezel, Anouk, Smeets, Harm J., and Maffia, Pasquale
- Subjects
- *
T cells , *ATHEROSCLEROSIS , *HYPERCHOLESTEREMIA , *MAST cells , *ANTIGEN presenting cells , *IMMUNITY - Abstract
Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4+ T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4+ T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet-fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide-loaded MCs increased OT-II CD4+ T cell proliferation in vitro. The aortic CD4+ and TH1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
14. LAT1 enables T cell activation under inflammatory conditions.
- Author
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Ogbechi, Joy, Wright, Helen L., Balint, Stefan, Topping, Louise M., Kristina, Zec, Huang, Yi-Shu, Pantazi, Eirini, Swart, Maarten, Windell, Dylan, Marin, Eros, Wempe, Michael F., Endou, Hitoshi, Thomas, Andrew M., Filer, Andrew, Stone, Trevor W., Clarke, Alexander J., Dustin, Michael L., and Williams, Richard O.
- Subjects
- *
T cells , *REGULATORY T cells , *JOINT pain , *T cell differentiation , *SYNOVIAL membranes , *EXPERIMENTAL arthritis , *T cell receptors , *ABATACEPT - Abstract
The aim of this study was to assess the L-type amino acid transporter-1 (LAT1) as a possible therapeutic target for rheumatoid arthritis (RA). Synovial LAT1 expression in RA was monitored by immunohistochemistry and transcriptomic datasets. The contribution of LAT1 to gene expression and immune synapse formation was assessed by RNA-sequencing and total internal reflection fluorescent (TIRF) microscopy, respectively. Mouse models of RA were used to assess the impact of therapeutic targeting of LAT1. LAT1 was strongly expressed by CD4+ T cells in the synovial membrane of people with active RA and the level of expression correlated with levels of ESR and CRP as well as DAS-28 scores. Deletion of LAT1 in murine CD4+ T cells inhibited the development of experimental arthritis and prevented the differentiation of CD4+ T cells expressing IFN-γ and TNF-α, without affecting regulatory T cells. LAT1 deficient CD4+ T cells demonstrated reduced transcription of genes associated with TCR/CD28 signalling, including Akt1, Akt2 , Nfatc2 , Nfkb1 and Nfkb2. Functional studies using TIRF microscopy revealed a significant impairment of immune synapse formation with reduced recruitment of CD3ζ and phospho-tyrosine signalling molecules in LAT1 deficient CD4+ T cells from the inflamed joints but not the draining lymph nodes of arthritic mice. Finally, it was shown that a small molecule LAT1 inhibitor, currently undergoing clinical trials in man, was highly effective in treating experimental arthritis in mice. It was concluded that LAT1 plays a critical role in activation of pathogenic T cell subsets under inflammatory conditions and represents a promising new therapeutic target for RA. • LAT1 is an amino acid transporter that has previously been shown to play a role in T cell activation. • This study shows that LAT1 is expressed by synovial T cells in rheumatoid arthritis and the level of expression correlates with disease severity. • LATI expression by T cells is required for development of severe arthritis in animal models. • Deletion of LAT1 impairs immune synapse formation by CD4+ T cells from the inflamed joint but not CD4+ T cells from the the lymph nodes. • The context-specific nature of LAT1 involvement in T cell activation makes it an ideal therapeutic target for treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
15. Hypercholesterolemia Induces a Mast Cell-CD4+ T Cell Interaction in Atherosclerosis
- Author
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Janine van Duijn, Maarten Swart, Bram Slütter, Johan Kuiper, Harm Smeets, Ilze Bot, Thomas van der Heijden, Eva Kritikou, Pasquale Maffia, Anouk Wezel, Kritikou, Eva, van der Heijden, Thoma, Swart, Maarten, van Duijn, Janine, Slütter, Bram, Wezel, Anouk, Smeets, Harm J, Maffia, Pasquale, Kuiper, Johan, and Bot, Ilze
- Subjects
Cell type ,T cell ,Immunology ,Proinflammatory cytokine ,LDL ,LDLr ,MC, mast cell ,MHC-II, MHC class II ,medicine ,Immunology and Allergy ,WTD, Westerntype diet ,MC ,oxLDL, oxidized LDL ,MHC-II ,Westerntype diet ,oxLDL ,CD86 ,MHC class II ,Innate immune system ,biology ,Chemistry ,Low-density lipoprotein ,LDL receptor ,Acquired immune system ,Mast cell ,humanities ,Cell biology ,LDLr, LDL receptor ,medicine.anatomical_structure ,oxidized LDL ,biology.protein ,WTD ,mast cell - Abstract
Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4+ T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4+ T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet–fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide–loaded MCs increased OT-II CD4+ T cell proliferation in vitro. The aortic CD4+ and TH1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis.
- Published
- 2019
16. Impact of SARS-CoV-2 spike stability and RBD exposure on antigenicity and immunogenicity.
- Author
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Rutten L, Swart M, Koornneef A, Bouchier P, Blokland S, Sadi A, Juraszek J, Vijayan A, Schmit-Tillemans S, Verspuij J, Choi Y, Daal CE, Perkasa A, Torres Morales S, Myeni SK, Kikkert M, Tolboom J, van Manen D, Kuipers H, Schuitemaker H, Zahn R, and Langedijk JPM
- Subjects
- Mice, Humans, Animals, SARS-CoV-2, COVID-19 Vaccines, Antibodies, Viral, Spike Glycoprotein, Coronavirus metabolism, Antibodies, Neutralizing, COVID-19 prevention & control, Viral Vaccines
- Abstract
The spike protein (S) of SARS-CoV-2 induces neutralizing antibodies and is the key component of current COVID-19 vaccines. The most efficacious COVID-19 vaccines are genetically-encoded spikes with a double proline substitution in the hinge region to stabilize S in the prefusion conformation (S-2P). A subunit vaccine can be a valuable addition to mRNA and viral vector-based vaccines but requires high stability of spike. In addition, further stabilization of the prefusion conformation of spike might improve immunogenicity. To test this, five spike proteins were designed and characterized, ranging from low to high stability. The immunogenicity of these proteins was assessed in mice, demonstrating that a spike (S-closed-2) with a high melting temperature, which still allowed ACE2 binding, induced the highest neutralization titers against homologous and heterologous strains (up to 16-fold higher than the least stabilized spike). In contrast, the most stable spike variant (S-locked), in which the receptor binding domains (RBDs) were locked in a closed conformation and thus not able to breathe, induced relatively low neutralizing antibody titers against heterologous strains. These data demonstrate that S protein stabilization with RBDs exposing highly conserved epitopes may be needed to increase the immunogenicity of spike proteins for future COVID-19 vaccines., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
17. Hypercholesterolemia Induces a Mast Cell-CD4 + T Cell Interaction in Atherosclerosis.
- Author
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Kritikou E, van der Heijden T, Swart M, van Duijn J, Slütter B, Wezel A, Smeets HJ, Maffia P, Kuiper J, and Bot I
- Subjects
- Animals, Cells, Cultured, Humans, Male, Mice, Mice, Knockout, Atherosclerosis immunology, CD4-Positive T-Lymphocytes immunology, Hypercholesterolemia immunology, Mast Cells immunology
- Abstract
Mast cells (MCs) are potent innate immune cells that aggravate atherosclerosis through the release of proinflammatory mediators inside atherosclerotic plaques. Similarly, CD4
+ T cells are constituents of the adaptive immune response and accumulate within the plaques following lipid-specific activation by APCs. Recently it has been proposed that these two cell types can interact in a direct manner. However, no indication of such an interaction has been investigated in the context of atherosclerosis. In our study, we aimed to examine whether MCs can act as APCs in atherosclerosis, thereby modulating CD4+ T cell responses. We observed that MCs increased their MHC class II expression under hyperlipidemic conditions both in vivo and in vitro. Furthermore, we showed that MCs can present Ags in vivo via MHC class II molecules. Serum from high-fat diet-fed mice also enhanced the expression of the costimulatory molecule CD86 on cultured MCs, whereas OVA peptide-loaded MCs increased OT-II CD4+ T cell proliferation in vitro. The aortic CD4+ and TH1 cell content of atherosclerotic mice that lack MCs was reduced as compared with their wild-type counterparts. Importantly, we identified MCs that express HLA-DR in advanced human atheromata, indicating that these cells are capable of Ag presentation within human atherosclerotic plaques. Therefore, in this artice, we show that MCs may directly modulate adaptive immunity by acting as APCs in atherosclerosis., (Copyright © 2019 by The American Association of Immunologists, Inc.)- Published
- 2019
- Full Text
- View/download PDF
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