Mechanisms that regulate macrophage burden in atherosclerosis

Circulation Research

Volumn 114, Issue 11, 2014, Pages 1757-1771

  Randolph, Gwendalyn J ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

atherosclerosis; macrophages; monocytes

Indexed keywords

APOLIPOPROTEIN E; CHOLESTEROL;

ADAPTIVE IMMUNITY; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; CELL PROLIFERATION; DENDRITIC CELL; DISEASE CLASSIFICATION; DISEASE COURSE; FOAM CELL; HUMAN; INNATE IMMUNITY; MACROPHAGE; MONOCYTE; MONONUCLEAR PHAGOCYTE; NONHUMAN; PRIORITY JOURNAL; RABBIT; REVIEW;

ATHEROSCLEROSIS; MACROPHAGES; MONOCYTES;

ANIMALS; ATHEROSCLEROSIS; CELL PROLIFERATION; DENDRITIC CELLS; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; FOAM CELLS; HUMANS; IMMUNITY, INNATE; MACROPHAGES; MICE; PLAQUE, ATHEROSCLEROTIC;

EID: 84901404011     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.114.301174     Document Type: Review

References (140)

1. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med. 1999;340:115-126.
2. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002;105:1135-1143.
3. van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994;89:36-44.
4. Farb A, Burke AP, Tang AL, Liang TY, Mannan P, Smialek J, Virmani R. Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996;93:1354-1363.
5. Glass CK, Witztum JL. Atherosclerosis the road ahead. Cell 2001;104:503-516.
6. Breslow JL. Mouse models of atherosclerosis. Science 1996;272:685-688.
7. Choi JH, Cheong C, Dandamudi DB, Park CG, Rodriguez A, Mehandru S, Velinzon K, Jung IH, Yoo JY, Oh GT, Steinman RM. Flt3 signalingdependent dendritic cells protect against atherosclerosis. Immunity 2011;35:819-831.
8. Herijgers N, Van Eck M, Groot PH, Hoogerbrugge PM, Van Berkel TJ. Effect of bone marrow transplantation on lipoprotein metabolism and atherosclerosis in LDL receptor-knockout mice. Arterioscler Thromb Vasc Biol. 1997;17:1995-2003.
9. Basavaraju SR, Easterly CE. Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. Med Phys. 2002;29:2391-2403.
10. Aparicio-Vergara M, Shiri-Sverdlov R, de Haan G, Hofker MH. Bone marrow transplantation in mice as a tool for studying the role of hematopoietic cells in metabolic and cardiovascular diseases. Atherosclerosis 2010;213:335-344.
11. Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI. Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med. 2006;203:2073-2083.
12. Koltsova EK, Garcia Z, Chodaczek G, Landau M, McArdle S, Scott SR, von Vietinghoff S, Galkina E, Miller YI, Acton ST, Ley K. Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis. J Clin Invest. 2012;122:3114-3126.
13. Mullick AE, Soldau K, Kiosses WB, Bell TA 3rd, Tobias PS, Curtiss LK. Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events. J Exp Med. 2008;205:373-383.
14. Rademakers T, Douma K, Hackeng TM, Post MJ, Sluimer JC, Daemen MJ, Biessen EA, Heeneman S, van Zandvoort MA. Plaque-associated vasa vasorum in aged apolipoprotein E-deficient mice exhibit proatherogenic functional features in vivo. Arterioscler Thromb Vasc Biol. 2013;33:249-256.
15. Haka AS, Potteaux S, Fraser H, Randolph GJ, Maxfield FR. Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy. PLoS One. 2012;7:e44823.
16. Lilledahl MB, Haugen OA, de Lange Davies C, Svaasand LO. Characterization of vulnerable plaques by multiphoton microscopy. J Biomed Opt. 2007;12:044005.
17. Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest. 2007;117:195-205.
18. Galkina E, Kadl A, Sanders J, Varughese D, Sarembock IJ, Ley K. Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependent. J Exp Med. 2006;203:1273-1282.
19. Doran AC, Lipinski MJ, Oldham SN, et al. B-cell aortic homing and atheroprotection depend on Id3. Circ Res. 2012;110:e1-e12.
20. Butcher MJ, Herre M, Ley K, Galkina E. Flow cytometry analysis of immune cells within murine aortas. J Vis Exp. 2011;1:2848.
21. Swirski FK, Pittet MJ, Kircher MF, Aikawa E, Jaffer FA, Libby P, Weissleder R. Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease. Proc Natl Acad Sci USA. 2006;103:10340-10345.
22. Llodrá J, Angeli V, Liu J, Trogan E, Fisher EA, Randolph GJ. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques. Proc Natl Acad Sci USA. 2004;101:11779-11784.
23. Trogan E, Feig JE, Dogan S, Rothblat GH, Angeli V, Tacke F, Randolph GJ, Fisher EA. Gene expression changes in foam cells and the role of chemokine receptor CCR7 during atherosclerosis regression in ApoEdeficient mice. Proc Natl Acad Sci USA. 2006;103:3781-3786.
24. Reis ED, Li J, Fayad ZA, Rong JX, Hansoty D, Aguinaldo JG, Fallon JT, Fisher EA. Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model. J Vasc Surg. 2001;34:541-547.
25. Chereshnev I, Trogan E, Omerhodzic S, Itskovich V, Aguinaldo JG, Fayad ZA, Fisher EA, Reis ED. Mouse model of heterotopic aortic arch transplantation. J Surg Res. 2003;111:171-176.
26. Martel C, Li W, Fulp B, Platt AM, Gautier EL, Westerterp M, Bittman R, Tall AR, Chen SH, Thomas MJ, Kreisel D, Swartz MA, Sorci-Thomas MG, Randolph GJ. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice. J Clin Invest. 2013;123:1571-1579.
27. Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, Garin A, Liu J, Mack M, van Rooijen N, Lira SA, Habenicht AJ, Randolph GJ. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest. 2007;117:185-194.
28. Potteaux S, Gautier EL, Hutchison SB, van Rooijen N, Rader DJ, Thomas MJ, Sorci-Thomas MG, Randolph GJ. Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/-mice during disease regression. J Clin Invest. 2011;121:2025-2036.
29. Randolph GJ. Emigration of monocyte-derived cells to lymph nodes during resolution of inflammation and its failure in atherosclerosis. Curr Opin Lipidol. 2008;19:462-468.
30. Millonig G, Niederegger H, Rabl W, Hochleitner BW, Hoefer D, Romani N, Wick G. Network of vascular-associated dendritic cells in intima of healthy young individuals. Arterioscler Thromb Vasc Biol. 2001;21:503-508.
31. Valladeau J, Duvert-Frances V, Pin JJ, Dezutter-Dambuyant C, Vincent C, Massacrier C, Vincent J, Yoneda K, Banchereau J, Caux C, Davoust J, Saeland S. The monoclonal antibody DCGM4 recognizes Langerin, a protein specific of Langerhans cells, and is rapidly internalized from the cell surface. Eur J Immunol. 1999;29:2695-2704.
32. Liu P, Yu YR, Spencer JA, Johnson AE, Vallanat CT, Fong AM, Patterson C, Patel DD. CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden. Arterioscler Thromb Vasc Biol. 2008;28:243-250.
33. Zhu SN, Chen M, Jongstra-Bilen J, Cybulsky MI. GM-CSF regulates intimal cell proliferation in nascent atherosclerotic lesions. J Exp Med. 2009;206:2141-2149.
34. Ginhoux F, Merad M. Ontogeny and homeostasis of Langerhans cells. Immunol Cell Biol. 2010;88:387-392.
35. Xiao H, Lu M, Lin TY, et al. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility. Circulation 2013;128:632-642.
36. Paulson KE, Zhu SN, Chen M, Nurmohamed S, Jongstra-Bilen J, Cybulsky MI. Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis. Circ Res. 2010;106:383-390.
37. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R, Shagdarsuren E, Lira SA, Weissman IL, Weber C, Jung S. CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 2009;113:963-972.
38. Jakubzick C, Tacke F, Ginhoux F, Wagers AJ, van Rooijen N, Mack M, Merad M, Randolph GJ. Blood monocyte subsets differentially give rise to CD103+ and CD103-pulmonary dendritic cell populations. J Immunol. 2008;180:3019-3027.
39. Choi JH, Do Y, Cheong C, Koh H, Boscardin SB, Oh YS, Bozzacco L, Trumpfheller C, Park CG, Steinman RM. Identification of antigen-presenting dendritic cells in mouse aorta and cardiac valves. J Exp Med. 2009;206:497-505.
40. Kniker WT, Cochrane CG. The localization of circulating immune complexes in experimental serum sickness. The role of vasoactive amines and hydrodynamic forces. J Exp Med. 1968;127:119-136.
41. Gautier EL, Shay T, Miller J, et al; Immunological Genome Consortium. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol. 2012;13:1118-1128.
42. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563-604.
43. Suzuki S, Honma K, Matsuyama T, Suzuki K, Toriyama K, Akitoyo I, Yamamoto K, Suematsu T, Nakamura M, Yui K, Kumatori A. Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha-dendritic cell development. Proc Natl Acad Sci USA. 2004;101:8981-8986.
44. Tamura T, Tailor P, Yamaoka K, Kong HJ, Tsujimura H, O'Shea JJ, Singh H, Ozato K. IFN regulatory factor-4 and-8 govern dendritic cell subset development and their functional diversity. J Immunol. 2005;174:2573-2581.
45. Schlitzer A, McGovern N, Teo P, et al. IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses. Immunity 2013;38:970-983.
46. Persson EK, Uronen-Hansson H, Semmrich M, Rivollier A, Hägerbrand K, Marsal J, Gudjonsson S, Håkansson U, Reizis B, Kotarsky K, Agace WW. IRF4 transcription-factor-dependent CD103(+)CD11b(+) dendritic cells drive mucosal T helper 17 cell differentiation. Immunity 2013;38:958-969.
47. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008;454:428-435.
48. Randolph GJ, Angeli V, Swartz MA. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nat Rev Immunol. 2005;5:617-628.
49. Jakubzick C, Tacke F, Llodra J, van Rooijen N, Randolph GJ. Modulation of dendritic cell trafficking to and from the airways. J Immunol. 2006;176:3578-3584.
50. Jakubzick C, Gautier EL, Gibbings SL, et al. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 2013;39:599-610.
51. Liuzzo G, Trotta F, Pedicino D. Interleukin-17 in atherosclerosis and cardiovascular disease: the good, the bad, and the unknown. Eur Heart J. 2013;34:556-559.
52. 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. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12:178-180.
53. Klingenberg R, Gerdes N, Badeau RM, et al. Depletion of FOXP3+ regulatory T cells promotes hypercholesterolemia and atherosclerosis. J Clin Invest. 2013;123:1323-1334.
54. Dansky HM, Charlton SA, Harper MM, Smith JD. T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci USA. 1997;94:4642-4646.
55. Reardon CA, Blachowicz L, White T, Cabana V, Wang Y, Lukens J, Bluestone J, Getz GS. Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21:1011-1016.
56. Gerrity RG. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981;103:181-190.
57. Qu C, Edwards EW, Tacke F, et al. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. J Exp Med. 2004;200:1231-1241.
58. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003;19:71-82.
59. Sunderkötter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol. 2004;172:4410-4417.
60. Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, Hoffmann R, Lang R, Haniffa M, Collin M, Tacke F, Habenicht AJ, Ziegler-Heitbrock L, Randolph GJ. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 2010;115:e10-e19.
61. Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol. 2007;81:584-592.
62. Carlin LM, Stamatiades EG, Auffray C, Hanna RN, Glover L, Vizcay-Barrena G, Hedrick CC, Cook HT, Diebold S, Geissmann F. Nr4a1-dependent Ly6C(low) monocytes monitor endothelial cells and orchestrate their disposal. Cell 2013;153:362-375.
63. Hanna RN, Shaked I, Hubbeling HG, Punt JA, Wu R, Herrley E, Zaugg C, Pei H, Geissmann F, Ley K, Hedrick CC. NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circ Res. 2012;110:416-427.
64. Hamers AA, Vos M, Rassam F, Marinkovi? G, Marincovic G, Kurakula K, van Gorp PJ, de Winther MP, Gijbels MJ, de Waard V, de Vries CJ. Bone marrow-specific deficiency of nuclear receptor Nur77 enhances atherosclerosis. Circ Res. 2012;110:428-438.
65. Chao LC, Soto E, Hong C, Ito A, Pei L, Chawla A, Conneely OM, Tangirala RK, Evans RM, Tontonoz P. Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice. J Lipid Res. 2013;54:806-815.
66. Randolph GJ, Sanchez-Schmitz G, Liebman RM, Schäkel K. The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting. J Exp Med. 2002;196:517-527.
67. Chapman CM, Beilby JP, McQuillan BM, Thompson PL, Hung J. Monocyte count, but not C-reactive protein or interleukin-6, is an independent risk marker for subclinical carotid atherosclerosis. Stroke 2004;35:1619-1624.
68. Johnsen SH, Fosse E, Joakimsen O, Mathiesen EB, Stensland-Bugge E, Njølstad I, Arnesen E. Monocyte count is a predictor of novel plaque formation: a 7-year follow-up study of 2610 persons without carotid plaque at baseline the Tromsø Study. Stroke 2005;36:715-719.
69. Yvan-Charvet L, Pagler T, Gautier EL, Avagyan S, Siry RL, Han S, Welch CL, Wang N, Randolph GJ, Snoeck HW, Tall AR. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 2010;328:1689-1693.
70. Murphy AJ, Akhtari M, Tolani S, Pagler T, Bijl N, Kuo CL, Wang M, Sanson M, Abramowicz S, Welch C, Bochem AE, Kuivenhoven JA, Yvan-Charvet L, Tall AR. ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice. J Clin Invest. 2011;121:4138-4149.
71. Ganda A, Magnusson M, Yvan-Charvet L, Hedblad B, Engström G, Ai D, Wang TJ, Gerszten RE, Melander O, Tall AR. Mild renal dysfunction and metabolites tied to low HDL cholesterol are associated with monocytosis and atherosclerosis. Circulation 2013;127:988-996.
72. Tolani S, Pagler TA, Murphy AJ, Bochem AE, Abramowicz S, Welch C, Nagareddy PR, Holleran S, Hovingh GK, Kuivenhoven JA, Tall AR. Hypercholesterolemia and reduced HDL-C promote hematopoietic stem cell proliferation and monocytosis: studies in mice and FH children. Atherosclerosis 2013;229:79-85.
73. Raffai RL. Apolipoprotein E regulation of myeloid cell plasticity in atherosclerosis. Curr Opin Lipidol. 2012;23:471-478.
74. Getz GS, Reardon CA. Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall. J Lipid Res. 2009;50(suppl):S156- S161.
75. Baitsch D, Bock HH, Engel T, Telgmann R, Müller-Tidow C, Varga G, Bot M, Herz J, Robenek H, von Eckardstein A, Nofer JR. Apolipoprotein E induces antiinflammatory phenotype in macrophages. Arterioscler Thromb Vasc Biol. 2011;31:1160-1168.
76. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013;13:709-721.
77. Ambarus CA, Krausz S, van Eijk M, Hamann J, Radstake TR, Reedquist KA, Tak PP, Baeten DL. Systematic validation of specific phenotypic markers for in vitro polarized human macrophages. J Immunol Methods 2012;375:196-206.
78. Dutta P, Courties G, Wei Y, et al. Myocardial infarction accelerates atherosclerosis. Nature 2012;487:325-329.
79. Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, Ramkhelawon B, Distel E, Westerterp M, Huang LS, Schmidt AM, Orchard TJ, Fisher EA, Tall AR, Goldberg IJ. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 2013;17:695-708.
80. Eberlé D, Luk FS, Kim RY, Olivas VR, Kumar N, Posada JM, Li K, Gaudreault N, Rapp JH, Raffai RL. Inducible ApoE gene repair in hypomorphic ApoE mice deficient in the low-density lipoprotein receptor promotes atheroma stabilization with a human-like lipoprotein profile. Arterioscler Thromb Vasc Biol. 2013;33:1759-1767.
81. Robbins CS, Hilgendorf I, Weber GF, et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nat Med. 2013;19:1166-1172.
82. Randolph GJ. Proliferating macrophages prevail in atherosclerosis. Nat Med 2013;19:1094-1095.
83. Subramanian M, Thorp E, Hansson GK, Tabas I. Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs. J Clin Invest. 2013;123:179-188.
84. Wu H, Gower RM, Wang H, Perrard XY, Ma R, Bullard DC, Burns AR, Paul A, Smith CW, Simon SI, Ballantyne CM. Functional role of CD11c+ monocytes in atherogenesis associated with hypercholesterolemia. Circulation 2009;119:2708-2717.
85. Macritchie N, Grassia G, Sabir SR, Maddaluno M, Welsh P, Sattar N, Ialenti A, Kurowska-Stolarska M, McInnes IB, Brewer JM, Garside P, Maffia P. Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2012;32:2569-2579.
86. Daissormont IT, Christ A, Temmerman L, et al. Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity. Circ Res. 2011;109:1387-1395.
87. Gomez D, Owens GK. Smooth muscle cell phenotypic switching in atherosclerosis. Cardiovasc Res. 2012;95:156-164.
88. Spann NJ, Garmire LX, McDonald JG, et al. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 2012;151:138-152.
89. Moore KJ, Kunjathoor VV, Koehn SL, Manning JJ, Tseng AA, Silver JM, McKee M, Freeman MW. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest. 2005;115:2192-2201.
90. Westerterp M, Murphy AJ, Wang M, et al. Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice. Cir Res. 2013;112:1456-1465.
91. Jakubzick C, Bogunovic M, Bonito AJ, Kuan EL, Merad M, Randolph GJ. Lymph-migrating, tissue-derived dendritic cells are minor constituents within steady-state lymph nodes. J Exp Med. 2008;205:2839-2850.
92. Ye M, Iwasaki H, Laiosa CV, Stadtfeld M, Xie H, Heck S, Clausen B, Akashi K, Graf T. Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential. Immunity 2003;19:689-699.
93. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11:155-161.
94. Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol. 2005;560:11-18.
95. Curtiss LK, Tobias PS. Emerging role of Toll-like receptors in atherosclerosis. J Lipid Res. 2009;50(suppl):S340-S345.
96. Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB, Arditi M. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci USA. 2004;101:10679-10684.
97. Lundberg AM, Ketelhuth DF, Johansson ME, Gerdes N, Liu S, Yamamoto M, Akira S, Hansson GK. Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis. Cardiovasc Res. 2013;99:364-373.
98. Berliner JA, Leitinger N, Tsimikas S. The role of oxidized phospholipids in atherosclerosis. J Lipid Res. 2009;50(suppl):S207-S212.
99. Kanters E, Pasparakis M, Gijbels MJ, Vergouwe MN, Partouns-Hendriks I, Fijneman RJ, Clausen BE, Förster I, Kockx MM, Rajewsky K, Kraal G, Hofker MH, de Winther MP. Inhibition of NF-κB activation in macrophages increases atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 2003;112:1176-1185.
100. Kanters E, Gijbels MJ, van der Made I, Vergouwe MN, Heeringa P, Kraal G, Hofker MH, de Winther MP. Hematopoietic NF-κB1 deficiency results in small atherosclerotic lesions with an inflammatory phenotype. Blood 2004;103:934-940.
101. Waterfield MR, Zhang M, Norman LP, Sun SC. NF-κB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase. Mol Cell 2003;11:685-694.
102. Guma M, Stepniak D, Shaked H, Spehlmann ME, Shenouda S, Cheroutre H, Vicente-Suarez I, Eckmann L, Kagnoff MF, Karin M. Constitutive intestinal NF-κb does not trigger destructive inflammation unless accompanied by MAPK activation. J Exp Med. 2011;208:1889-1900.
103. Sikorski K, Chmielewski S, Olejnik A, Wesoly JZ, Heemann U, Baumann M, Bluyssen H. STAT1 as a central mediator of IFNγ and TLR4 signal integration in vascular dysfunction. JAKSTAT. 2012;1:241-249.
104. Gupta S, Pablo AM, Jiang Xc, Wang N, Tall AR, Schindler C. IFNgamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest. 1997;99:2752-2761.
105. Lim WS, Timmins JM, Seimon TA, Sadler A, Kolodgie FD, Virmani R, Tabas I. Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo. Circulation 2008;117:940-951.
106. Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 2010;464:1357-1361.
107. Ng TM, Monack DM. Revisiting caspase-11 function in host defense. Cell Host Microbe. 2013;14:9-14.
108. Rajamäki K, Lappalainen J, Oörni K, Välimäki E, Matikainen S, Kovanen PT, Eklund KK. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One. 2010;5:e11765.
109. Menu P, Pellegrin M, Aubert JF, Bouzourene K, Tardivel A, Mazzolai L, Tschopp J. Atherosclerosis in ApoE-deficient mice progresses independently of the NLRP3 inflammasome. Cell Death Dis. 2011;2:e137.
110. Freigang S, Ampenberger F, Weiss A, Kanneganti TD, Iwakura Y, Hersberger M, Kopf M. Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis. Nat Immunol. 2013;14:1045-1053.
111. Hannedouche S, Zhang J, Yi T, et al. Oxysterols direct immune cell migration via EBI2. Nature 2011;475:524-527.
112. Liu C, Yang XV, Wu J, Kuei C, Mani NS, Zhang L, Yu J, Sutton SW, Qin N, Banie H, Karlsson L, Sun S, Lovenberg TW. Oxysterols direct B-cell migration through EBI2. Nature 2011;475:519-523.
113. Gatto D, Paus D, Basten A, Mackay CR, Brink R. Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity 2009;31:259-269.
114. Gatto D, Wood K, Caminschi I, Murphy-Durland D, Schofield P, Christ D, Karupiah G, Brink R. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat Immunol. 2013;14:446-453.
115. Kelly LM, Pereira JP, Yi T, Xu Y, Cyster JG. EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues. J Immunol. 2011;187:3026-3032.
116. Pereira JP, Kelly LM, Xu Y, Cyster JG. EBI2 mediates B cell segregation between the outer and centre follicle. Nature 2009;460:1122-1126.
117. Yi T, Cyster JG. EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture. Elife. 2013;2:e00757.
118. Yvan-Charvet L, Welch C, Pagler TA, Ranalletta M, Lamkanfi M, Han S, Ishibashi M, Li R, Wang N, Tall AR. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions. Circulation 2008;118:1837-1847.
119. Zhu X, Owen JS, Wilson MD, Li H, Griffiths GL, Thomas MJ, Hiltbold EM, Fessler MB, Parks JS. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol. J Lipid Res. 2010;51:3196-3206.
120. Randolph GJ, Ochando J, Partida-Sanchez S. Migration of dendritic cells and their precursors. Annu Rev Immunol. 2008;26:293-316.
121. Thorp E, Subramanian M, Tabas I. The role of macrophages and dendritic cells in the clearance of apoptotic cells in advanced atherosclerosis. Eur J Immunol. 2011;41:2515-2518.
122. Hochreiter-Hufford A, Ravichandran KS. Clearing the dead: apoptotic cell sensing, recognition, engulfment, and digestion. Cold Spring Harb Perspect Biol. 2013;5:a008748.
123. Gautier EL, Huby T, Witztum JL, Ouzilleau B, Miller ER, Saint-Charles F, Aucouturier P, Chapman MJ, Lesnik P. Macrophage apoptosis exerts divergent effects on atherogenesis as a function of lesion stage. Circulation 2009;119:1795-1804.
124. Shearn AI, Deswaerte V, Gautier EL, Saint-Charles F, Pirault J, Bouchareychas L, Rucker EB 3rd, Beliard S, Chapman J, Jessup W, Huby T, Lesnik P. Bcl-x inactivation in macrophages accelerates progression of advanced atherosclerotic lesions in Apoe(-/-) mice. Arterioscler Thromb Vasc Biol. 2012;32:1142-1149.
125. Gerrity RG. The role of the monocyte in atherogenesis: II. Migration of foam cells from atherosclerotic lesions. Am J Pathol. 1981;103:191-200.
126. Niess JH, Brand S, Gu X, Landsman L, Jung S, McCormick BA, Vyas JM, Boes M, Ploegh HL, Fox JG, Littman DR, Reinecker HC. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 2005;307:254-258.
127. Calderon B, Suri A, Miller MJ, Unanue ER. Dendritic cells in islets of Langerhans constitutively present beta cell-derived peptides bound to their class II MHC molecules. Proc Natl Acad Sci USA. 2008;105:6121-6126.
128. Angeli V, Llodrá J, Rong JX, Satoh K, Ishii S, Shimizu T, Fisher EA, Randolph GJ. Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity 2004;21:561-574.
129. Bellingan GJ, Caldwell H, Howie SE, Dransfield I, Haslett C. In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J Immunol. 1996;157:2577-2585.
130. Gautier EL, Ivanov S, Lesnik P, Randolph GJ. Local apoptosis mediates clearance of macrophages from resolving inflammation in mice. Blood 2013;122:2714-2722.
131. Feig JE, Pineda-Torra I, Sanson M, et al. LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression. J Clin Invest. 2010;120:4415-4424.
132. Feig JE, Rong JX, Shamir R, Sanson M, Vengrenyuk Y, Liu J, Rayner K, Moore K, Garabedian M, Fisher EA. HDL promotes rapid atherosclerosis regression in mice and alters inflammatory properties of plaque monocyte-derived cells. Proc Natl Acad Sci USA. 2011;108:7166-7171.
133. van Gils JM, Derby MC, Fernandes LR, et al. The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques. Nat Immunol. 2012;13:136-143.
134. Feig JE, Shang Y, Rotllan N, Vengrenyuk Y, Wu C, Shamir R, Torra IP, Fernandez-Hernando C, Fisher EA, Garabedian MJ. Statins promote the regression of atherosclerosis via activation of the CCR7-dependent emigration pathway in macrophages. PLoS One. 2011;6:e28534.
135. Wan W, Lionakis MS, Liu Q, Roffê E, Murphy PM. Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice. Cardiovasc Res. 2013;97:580-588.
136. Luchtefeld M, Grothusen C, Gagalick A, Jagavelu K, Schuett H, Tietge UJ, Pabst O, Grote K, Drexler H, Förster R, Schieffer B. Chemokine receptor 7 knockout attenuates atherosclerotic plaque development. Circulation 2010;122:1621-1628.
137. Van Craeyveld E, Gordts SC, Nefyodova E, Jacobs F, De Geest B. Regression and stabilization of advanced murine atherosclerotic lesions: a comparison of LDL lowering and HDL raising gene transfer strategies. J Mol Med (Berl). 2011;89:555-567.
138. Wendland M, Willenzon S, Kocks J, Davalos-Misslitz AC, Hammerschmidt SI, Schumann K, Kremmer E, Sixt M, Hoffmeyer A, Pabst O, Förster R. Lymph node T cell homeostasis relies on steady state homing of dendritic cells. Immunity 2011;35:945-957.
139. Egen JG, Rothfuchs AG, Feng CG, Winter N, Sher A, Germain RN. Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas. Immunity 2008;28:271-284.
140. Miller JC, Brown BD, Shay T, et al; Immunological Genome Consortium. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol. 2012;13:888-899.