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Virchows Archiv
Published in: Virchows Archiv 2/2011

01-02-2011 | Review and Perspective

Current advances in understanding of immunopathology of atherosclerosis

Authors: Colin-John Perrins, Yuri V. Bobryshev

Published in: Virchows Archiv | Issue 2/2011

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Abstract

The importance of the involvement of the immune system in the development and progression of atherosclerosis was first suggested after the discovery of T cells in atherosclerotic lesions in 1990s. In order to be activated, T cell needs to be presented with an antigen but how this occurs in atherosclerosis has been unclear until recently. Current research has recognised dendritic cells as key initiators and regulators of immune processes in atherosclerosis. Accumulating evidence has revealed novel functions of several subsets of regulatory T cells, which have been shown to maintain immunological tolerance to self-antigens and to inhibit atherosclerosis development by suppressing the inflammatory response of effector T cells. Recent studies have also revealed the importance of natural killer T cells and their interaction with dendritic cells in atherogenesis. This review briefly summarises recent advances in the understanding of immune mechanisms in atherosclerosis and highlights the perspective of immunisation as an approach against this disease.
Literature
1.
Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK (1986) Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 6:131–138PubMed
2.
Hansson GK, Holm J, Jonasson L (1989) Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 135:169–175PubMed
3.
Hansson GK, Jonasson L (2009) The discovery of cellular immunity in the atherosclerotic plaque. Arterioscler Thromb Vasc Biol 29:1714–1717CrossRefPubMed
4.
Hansson GK (2009) Atherosclerosis—an immune disease: the Anitschkov Lecture 2007. Atherosclerosis 202:2–10CrossRefPubMed
5.
Zhou X, Nicoletti A, Elhage R, Hansson GK (2000) Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation 102:2919–2922PubMed
6.
Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, Flavell RA, Hansson GK, Klatzmann D, Tedgui A, Mallat Z (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12:178–180CrossRefPubMed
7.
Mallat Z, Gojova A, Brun V, Esposito B, Fournier N, Cottrez F, Tedgui A, Groux H (2003) Induction of a regulatory T cell type 1 response reduces the development of atherosclerosis in apolipoprotein E-knockout mice. Circulation 108:1232–1237CrossRefPubMed
8.
Mor A, Planer D, Luboshits G, Afek A, Metzger S, Chajek-Shaul T, Keren G, George J (2007) Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. Arterioscler Thromb Vasc Biol 27:893–900, 2007CrossRefPubMed
9.
Whitham S, Ramsamy T (2006) articipatory role of natural killer and natural killer T cells in atherosclerosis: lessons learned from in vivo mouse studies. Canad J Physiol Pharmacol 84:67–75CrossRef
10.
Bobryshev YV, Lord RS (1995) Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of vascular dendritic cells in athero-resistant and athero-prone areas of the normal aorta. Arch Histol Cytol 58:307–322CrossRefPubMed
11.
Bobryshev YV, Lord RS (1998) Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions. Cardiovasc Res 37:799–810CrossRefPubMed
12.
13.
Stoll G, Bendszus M (2006) Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 37:1923–1932CrossRefPubMed
14.
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809CrossRefPubMed
15.
Lord RS, Bobryshev YV (2002) Hallmarks of atherosclerotic lesion development with special reference to immune inflammatory mechanisms. Cardiovasc Surg 10:405–414CrossRefPubMed
16.
Millonig G, Schwentner C, Mueller P, Mayerl C, Wick G (2001) The vascular-associated lymphoid tissue: a new site of local immunity. Curr Opin Lipidol 12:547–553CrossRefPubMed
17.
Wick G, Knoflach M, Xu Q (2004) Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 22:361–403CrossRefPubMed
18.
Bobryshev YV (2006) Monocyte recruitment and foam cell formation in atherosclerosis. Micron 37:208–222CrossRefPubMed
19.
Niessner A, Goronzy JJ, Weyand CM (2007) Immune-mediated mechanisms in atherosclerosis: prevention and treatment of clinical manifestations. Curr Pharm Des 13:3701–3710CrossRefPubMed
20.
Steinman R, Adams J, Cohn Z (1973) Identification of a novel cell type in peripheral lymphoid organs of mice, morphology, quantitation, tissue distribution. J Exp Med 137:1142–1162CrossRefPubMed
21.
Lotze M, Thomson A (2001) Dendritic cells: biology and clinical applications, Ed 2nd edn. Academic, San Diego, California, USA
22.
Bobryshev YV (2005) Dendritic cells in atherosclerosis: current status of the problem and clinical relevance. Eur Heart J 26:1700–1704CrossRefPubMed
23.
Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI (2006) Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med 203:2073–2083CrossRefPubMed
24.
Choi JH, Do Y, Cheong C, Koh H, Boscardin SB, Oh YS, Bozzacco L, Trumpfheller C, Park CG, Steinman RM (2009) Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med 206:479–505CrossRef
25.
Randolph GJ, Potteaux S (2010) Vascular dendritic cells as gatekeepers of lipid accumulation within nascent atherosclerotic plaques. Circ Res 106:227–229CrossRefPubMed
26.
Lipscomb M, Masten B (2002) Dendritic cells: immune regulators in health and disease. Physiol Rev 82:97–130PubMed
27.
Steinman R, Hawiger D, Nussenzweig M (2003) Tolerogenic dendritic cells. Ann Rev Immunol 21:685–711CrossRef
28.
Heath W, Belz G, Behrens G (2004) Cross-presentation, dendritic cell subsets and the generation of immunity to cellular agents. Immunol Rev 199:9–26CrossRefPubMed
29.
de Jong E, Smits H, Kapsenberg M (2005) Dendritic cell-mediated T cell polarization. Springer Semin Immunopathol 26:289–307CrossRefPubMed
30.
Gelin C, Sloma I, Charron D, Mooney N (2006) Regulation of MHC II and CD1 antigen presentation: from ubiquity to security. J Leukoc Biol 85:215–224, 2009CrossRef
31.
32.
Bobryshev YV, Taksir T, Lord RS, Freeman MW (2001) Evidence that dendritic cells infiltrate atherosclerotic lesions in apolipoprotein E-deficient mice. Histol Histopathol 16:801–808PubMed
33.
Ozmen J, Bobryshev YV, Lord RS, Ashwell KW (2002) Identification of dendritic cells in aortic atherosclerotic lesions in rats with diet-induced hypercholesterolaemia. Histol Histopathol 17:223–237PubMed
34.
Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K, Iyoda T, Ravetch J, Dhodapkar M, Inaba K, Nussenzweig M (2003) Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann NY Acad Sci 987:15–25CrossRefPubMed
35.
Naik SH, Metcalf D, van Nieuwenhuijze A, Wicks I, Wu L, O'Keeffe M, Shortman K (2006) Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol 7:663–671CrossRefPubMed
36.
Shortman K, Naik S (2007) Steady-state and inflammatory dendritic cell development. Nat Rev Immunol 7:19CrossRefPubMed
37.
Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, Di Pucchio T, Connolly J, Fay JW, Pascual V, Palucka AK, Banchereau J (2007) Dendritic cell subsets in health and disease. Immunol Rev 219:118–142CrossRefPubMed
38.
Wilson NS, El-Sukkari D, Belz GT, Smith CM, Steptoe RJ, Heath WR, Shortman K, Villadangos JA (2003) Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood 102:2187–2194CrossRefPubMed
39.
Auffray C, Sieweke M, Geissmann F (2003) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Ann Rev Immunol 27:669–692CrossRef
40.
Gautier EL, Huby T, Saint-Charles F, Ouzilleau B, Pirault J, Deswaerte V, Ginhoux F, Miller ER, Witztum JL, Chapman MJ, Lesnik P (2009) Conventional dendritic cells at the crossroads between immunity and cholesterol homeostasis in atherosclerosis. Circulation 119:2367–2375CrossRefPubMed
41.
Wang L, Li D, Yang K, Hu Y, Zeng Q (2008) Toll-like receptor 4 and mitogen-activated protein kinase signal system are involved in activation of dendritic cells in patients with acute coronary syndrome. Immunology 125:122–130CrossRefPubMed
42.
Paulson KE, Zhu SN, Chen M, Nurmohamed S, Jongstra-Bilen J, Cybulsky MI (2010) Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis. Circ Res 106:383–390CrossRefPubMed
43.
Ludewig B, Freigang S, Jäggi M, Kurrer MO, Pei YC, Vlk L, Odermatt B, Zinkernagel RM, Hengartner H (2000) Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model. Proc Natl Acad Sci USA 97:12752–12757CrossRefPubMed
44.
Angeli V, Llodrá J, Rong JX, Satoh K, Ishii S, Shimizu T, Fisher EA, Randolph GJ (2004) Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilisation. Immunity 21:561–574CrossRefPubMed
45.
Packard RR, Maganto-García E, Gotsman I, Tabas I, Libby P, Lichtman AH (2008) CD11c(+) dendritic cells maintain antigen processing presentation capabilities and CD4(+) T-cell priming efficacy under hypercholesterolemia conditions. Circ Res 103:965–973CrossRefPubMed
46.
Habets KL, van Puijvelde GH, van Duivenvoorde LM, van Wanrooij EJ, de Vos P, Tervaert JW, van Berkel TJ, Toes RE, Kuiper J (2010) Vaccination using oxidised low-density lipoproteins-pulsed dendritic cells reduces atherosclerosis in LDL receptor-deficient mice. Cardiovasc Res 85:622–630CrossRefPubMed
47.
Hjerpe C, Johansson D, Hermansson A, Hansson GK, Zhou X (2010) Dendritic cells pulsed with melondialdehyde modified low density lipoprotein aggravate atherosclerosis in ApoE (−/−) mice. Atherosclerosis 209:436–441CrossRefPubMed
48.
van Es T, van Puijvelde GH, Foks AC, Habets KL, Bot I, Gilboa E, Van Berkel TJ, Kuiper J (2010) Vaccination against Foxp3(+) regulatory T cells aggravates atherosclerosis. Atherosclerosis 209:74–80CrossRefPubMed
49.
Alderman CJ, Bunyard PR, Chain BM, Foreman JC, Leake DS, Katz DR (2002) Effects of oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment? Cardiovasc Res 55:806–819CrossRefPubMed
50.
51.
Doherty TM, Fisher EA, Arditi M (2006) TLR signaling and trapped vascular dendritic cells in the development of atherosclerosis. Trends Immunol 27:222–227CrossRefPubMed
52.
Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336, 2007CrossRefPubMed
53.
Erbel C, Sato K, Meyer FB, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM (2007) Functional profile of activated dendritic cells in unstable atherosclerotic plaque. Basic Res Cardiol 102:123–132CrossRefPubMed
54.
Yilmaz A, Lochno M, Traeg F, Cicha I, Reiss C, Stumpf C, Raaz D, Anger T, Amann K, Probst T, Ludwig J, Daniel WG, Garlichs CD (2004) Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis 176:85–93CrossRef
55.
Asselin-Paturel C, Trinchieri G (2005) Production of type I interferons: plasmacytoid dendritic cells and beyond. J Exp Med 202:461–465CrossRefPubMed
56.
Decker T, Muller M, Stockinger S (2005) The yin and yang of type I interferon activity in bacterial infection. Nat Rev Immunol 5:675–687CrossRefPubMed
57.
Van Vré EA, Hoymans VY, Bult H, Lenjou M, Van Bockstaele DR, Vrints CJ, Bosmans JM (2006) Decreased number of circulating plasmacytoid dendritic cells in patients with atherosclerotic coronary artery disease. Coron Artery Dis 17:243–248CrossRefPubMed
58.
Bobryshev YV, Lord RS (2005) Co-accumulation of dendritic cells and natural killer T cells within rupture-prone regions in human atherosclerotic plaques. J Histochem Cytochem 53:781–785CrossRefPubMed
59.
Lee T, Yen H, Pan C, Chau L (1999) The role of interleukin 12 in the development of atherosclerosis in ApoE-deficient mice. Atheroscler Thromb Vasc Biol 19:734–742
60.
Davenport P, Tipping P (2003) The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol 163:1117–1125CrossRefPubMed
61.
Caligiuri G, Rudling M, Ollivier V, Jacob MP, Michel JB, Hansson GK, Nicoletti A (2003) Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low-density lipoproteins in apolipoprotein E knockout mice. Mol Med 9:10–17PubMed
62.
Pinderski L, Fyfe A, Hedrick C, Olvera T (1999) Interleukin-10 blocks atherosclerotic events in vitro and in vivo. Atheroscler ThrombVasc Biol 19:2847–2853
63.
Aslanian A, Chapman H, Charo I (2005) Transient role for CD1d-restricted natural killer T cells in the formation of atherosclerotic lesions. Atheroscler ThrombVasc Biol 25:628–632CrossRef
64.
Whitman SC, Rateri DL, Szilvassy SJ, Yokoyama W, Daugherty A (2004) Depletion of natural killer cell function decreases atherosclerosis in low-density lipoprotein receptor null mice. Arterioscler Thromb Vasc Biol 24:1049–1054CrossRefPubMed
65.
Van Kaer L (2007) NKT cells: T lymphocytes with innate effector functions. Curr Opin Immunol 19:354–364CrossRefPubMed
66.
Bezbradica JS, Stanic AK, Matsuki N, Bour-Jordan H, Bluestone JA, Thomas JW, Unutmaz D, Van Kaer L, Joyce S (2005) Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J Immunol 174:4694–4705
67.
Schmieg J, Yang G, Franck RW, Van Rooijen N, Tsuji M (2005) Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion. Proc Natl Acad Sci USA 102:1127–1132CrossRefPubMed
68.
Van Kaer L (2004) Natural killer T cells as targets for immunotherapy of autoimmune diseases. Immunol Cell Biol 82:315–322CrossRefPubMed
69.
Hansson G, Nilsson J (2009) Vaccination against atherosclerosis? Induction of atheroprotective immunity. Semin Immunopathol 31:95–101CrossRefPubMed
70.
Palinski W, Milller E, Witztum J (1995) Immunisation of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. Proc Natl Acad Sci USA 92:821–825CrossRefPubMed
71.
Binder CJ, Hartvigsen K, Witztum JL (2007) Promise of immune modulation to inhibit atherogenesis. J Am Coll Cardiol 50:547–550CrossRefPubMed
72.
Nilsson J, Nordin Fredrikson G, Schiopu A, Shah PK, Jansson B, Carlsson R (2007) Oxidized LDL antibodies in treatment and risk assessment of atherosclerosis and associated cardiovascular disease. Curr Pharm Des 13:1021–1030CrossRefPubMed
73.
Fredrikson GN, Björkbacka H, Söderberg I, Ljungcrantz I, Nilsson J (2008) Treatment with apo B peptide vaccines inhibits atherosclerosis in human apo B-100 transgenic mice without inducing an increase in peptide-specific antibodies. J Intern Med 264:563–570CrossRefPubMed
74.
van Leeuwen M, Damoiseaux J, Duijvestijn A, Tervaert JW (2009) The therapeutic potential of targeting B cells and anti-oxLDL antibodies in atherosclerosis. Autoimmun Rev 9:53–57CrossRefPubMed
75.
Bobryshev YV (2001) Can dendritic cells be exploited for therapeutic intervention in atherosclerosis? Atherosclerosis 154:511–512CrossRefPubMed
76.
Markiewicz M, Kast W (2004) Progress in the development of immunotherapy of cancer using ex vivo-generated dendritic cells expressing multiple tumor antigen epitopes. Cancer Investig 22:417–434CrossRef
77.
Dubsky P, Ueno H, Piqueras B, Connolly J, Banchereau J, Palucka AK (2005) Human dendritic cell subsets for vaccination. J Clin Immunol 25:551–572CrossRefPubMed
78.
Benko S, Magyarics Z, Szabó A, Rajnavölgyi E (2008) Dendritic cell subtypes as primary targets of vaccines: the emerging role and cross-talk of pattern recognition receptors. Biol Chem 389:469–485CrossRefPubMed
79.
Steinman RM (2008) Dendritic cells in vivo: a key target for a new vaccine science. Immunity 29:319–324CrossRefPubMed
Metadata
Title
Current advances in understanding of immunopathology of atherosclerosis
Authors
Colin-John Perrins
Yuri V. Bobryshev
Publication date
01-02-2011
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 2/2011
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-010-1006-5

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