Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver

Circulation Research

Volumn 120, Issue 11, 2017, Pages 1740-1753

  Mailer, Reiner K W ^a   Gisterå, Anton ^a   Polyzos, Konstantinos A ^a   Ketelhuth, Daniel F J ^a   Hansson, Göran K ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

atherosclerosis; hypercholesterolemia; inflammation; liver; metabolism; regulatory T cells; transforming growth factor beta

Indexed keywords

CD11B ANTIGEN; GLYCOPROTEIN P 15095; TRANSFORMING GROWTH FACTOR BETA1;

ADOPTIVE TRANSFER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATHEROSCLEROSIS; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL PROLIFERATION; CHOLESTEROL INTAKE; CHRONIC LIVER DISEASE; COMPARATIVE STUDY; CONTROLLED STUDY; HYPERCHOLESTEROLEMIA; IMMUNE RESPONSE; LIVER CELL; MOUSE; NONALCOHOLIC FATTY LIVER; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; TH1 CELL; TH17 CELL; WESTERN DIET; ANIMAL; BLOOD; C57BL MOUSE; CYTOLOGY; LIVER; PATHOLOGY; PHYSIOLOGY; RANDOMIZATION; TRANSGENIC MOUSE;

ANIMALS; CELL DIFFERENTIATION; HYPERCHOLESTEROLEMIA; LIVER; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; RANDOM ALLOCATION; T-LYMPHOCYTES, REGULATORY;

EID: 85018469572     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.116.310054     Document Type: Article

References (58)

1. Lüth S, Huber S, Schramm C, Buch T, Zander S, Stadelmann C, Brück W, Wraith DC, Herkel J, Lohse AW. Ectopic expression of neural autoantigen in mouse liver suppresses experimental autoimmune neuroinflammation by inducing antigen-specific Tregs. J Clin Invest. 2008;118:3403-3410. doi: 10.1172/JCI32132.
2. Carambia A, Freund B, Schwinge D, Heine M, Laschtowitz A, Huber S, Wraith DC, Korn T, Schramm C, Lohse AW, Heeren J, Herkel J. TGF-dependent induction of CD4CD25Foxp3 Tregs by liver sinusoidal endothelial cells. J Hepatol. 2014;61:594-599. doi: 10.1016/j. jhep.2014.04.027.
3. Wong MC, van Diepen JA, Hu L, et al. Hepatocyte-specific IKK expression aggravates atherosclerosis development in APOE 3-Leiden mice. Atherosclerosis. 2012;220:362-368. doi: 10.1016/j. atherosclerosis.2011.06.055.
4. Luchtefeld M, Schunkert H, Stoll M, et al. Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man. J Exp Med. 2007;204:1935-1944. doi: 10.1084/jem.20070120.
5. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12:204-212. doi: 10.1038/ni.2001.
6. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057-1061. doi: 10.1126/science.1079490.
7. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med. 2003;198:1875-1886. doi: 10.1084/jem.20030152.
8. 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. doi: 10.1172/JCI63891.
9. Mor A, Planer D, Luboshits G, Afek A, Metzger S, Chajek-Shaul T, Keren G, George J. Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:893-900. doi: 10.1161/01.ATV.0000259365.31469.89.
10. 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. doi: 10.1038/nm1343.
11. Zhou X, Robertson AK, Hjerpe C, Hansson GK. Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis. Arterioscler Thromb Vasc Biol. 2006;26:864-870. doi: 10.1161/01.ATV.0000206122.61591.ff.
12. Hermansson A, Ketelhuth DF, Strodthoff D, Wurm M, Hansson EM, Nicoletti A, Paulsson-Berne G, Hansson GK. Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis. J Exp Med. 2010;207:1081-1093. doi: 10.1084/jem.20092243.
13. Li Z, Soloski MJ, Diehl AM. Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. Hepatology. 2005;42:880-885. doi: 10.1002/hep.20826.
14. Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J, Eberl G, Hamann A, Wagner H, Huehn J, Sparwasser T. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med. 2007;204:57-63. doi: 10.1084/jem.20061852.
15. Mailer RK, Falk K, Rötzschke O. Absence of leucine zipper in the natural FOXP3Delta2Delta7 isoform does not affect dimerization but abrogates suppressive capacity. PLoS One. 2009;4:e6104. doi: 10.1371/journal. pone.0006104.
16. Mailer RK, Joly AL, Liu S, Elias S, Tegner J, Andersson J. IL-1 promotes Th17 differentiation by inducing alternative splicing of FOXP3. Sci Rep. 2015;5:14674. doi: 10.1038/srep14674.
17. van Loosdregt J, Coffer PJ. Post-translational modification networks regulating FOXP3 function. Trends Immunol. 2014;35:368-378. doi: 10.1016/j.it.2014.06.005.
18. Yadav M, Louvet C, Davini D, Gardner JM, Martinez-Llordella M, Bailey-Bucktrout S, Anthony BA, Sverdrup FM, Head R, Kuster DJ, Ruminski P, Weiss D, Von Schack D, Bluestone JA. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med. 2012;209:1713-22, S1. doi: 10.1084/jem.20120822.
19. Weiss JM, Bilate AM, Gobert M, et al. Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med. 2012;209:1723-42, S1. doi: 10.1084/ jem.20120914.
20. Glinka Y, Prud'homme GJ. Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity. J Leukoc Biol. 2008;84:302-310. doi: 10.1189/jlb.0208090.
21. Getz GS, Reardon CA. The mutual interplay of lipid metabolism and the cells of the immune system in relation to atherosclerosis. Clin Lipidol. 2014;9:657-671. doi: 10.2217/clp.14.50.
22. Hermansson A, Johansson DK, Ketelhuth DF, Andersson J, Zhou X, Hansson GK. Immunotherapy with tolerogenic apolipoprotein B-100-loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice. Circulation. 2011;123:1083-1091. doi: 10.1161/ CIRCULATIONAHA.110.973222.
23. Klingenberg R, Ketelhuth DF, Strodthoff D, Gregori S, Hansson GK. Subcutaneous immunization with heat shock protein-65 reduces atherosclerosis in Apoe/ mice. Immunobiology. 2012;217:540-547. doi: 10.1016/j.imbio.2011.06.006.
24. Nishioka T, Shimizu J, Iida R, Yamazaki S, Sakaguchi S. CD4+CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice. J Immunol. 2006;176:6586-6593.
25. Scheffold A, Hühn J, Höfer T. Regulation of CD4+CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur J Immunol. 2005;35:1336-1341. doi: 10.1002/eji.200425887.
26. Frutkin AD, Otsuka G, Stempien-Otero A, Sesti C, Du L, Jaffe M, Dichek HL, Pennington CJ, Edwards DR, Nieves-Cintrón M, Minter D, Preusch M, Hu JH, Marie JC, Dichek DA. TGF-[beta]1 limits plaque growth, stabilizes plaque structure, and prevents aortic dilation in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2009;29:1251-1257. doi: 10.1161/ ATVBAHA.109.186593.
27. Lievens D, Habets KL, Robertson AK, et al. Abrogated transforming growth factor beta receptor II (TGFRII) signalling in dendritic cells promotes immune reactivity of T cells resulting in enhanced atherosclerosis. Eur Heart J. 2013;34:3717-3727. doi: 10.1093/eurheartj/ehs106.
28. Li D, Liu Y, Chen J, Velchala N, Amani F, Nemarkommula A, Chen K, Rayaz H, Zhang D, Liu H, Sinha AK, Romeo F, Hermonat PL, Mehta JL. Suppression of atherogenesis by delivery of TGFbeta1ACT using adenoassociated virus type 2 in LDLR knockout mice. Biochem Biophys Res Commun. 2006;344:701-707. doi: 10.1016/j.bbrc.2006.04.010.
29. Mallat Z, Gojova A, Marchiol-Fournigault C, Esposito B, Kamaté C, Merval R, Fradelizi D, Tedgui A. Inhibition of transforming growth factorbeta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ Res. 2001;89:930-934.
30. Grainger DJ, Mosedale DE, Metcalfe JC, Böttinger EP. Dietary fat and reduced levels of TGFbeta1 act synergistically to promote activation of the vascular endothelium and formation of lipid lesions. J Cell Sci. 2000;113 (pt 13):2355-2361.
31. Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK. Disruption of TGF-beta signaling in T cells accelerates atherosclerosis. J Clin Invest. 2003;112:1342-1350. doi: 10.1172/JCI18607.
32. Zhou X, Johnston TP, Johansson D, Parini P, Funa K, Svensson J, Hansson GK. Hypercholesterolemia leads to elevated TGF-beta1 activity and T helper 3-dependent autoimmune responses in atherosclerotic mice. Atherosclerosis. 2009;204:381-387. doi: 10.1016/j. atherosclerosis.2008.10.017.
33. Lochner M, Wang Z, Sparwasser T. The special relationship in the development and function of T helper 17 and regulatory T cells. Prog Mol Biol Transl Sci. 2015;136:99-129. doi: 10.1016/bs.pmbts.2015.07.013.
34. Ng HP, Burris RL, Nagarajan S. Attenuated atherosclerotic lesions in apoE-Fc-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells. J Immunol. 2011;187:6082-6093. doi: 10.4049/jimmunol.1004133.
35. Roth-Eichhorn S, Kühl K, Gressner AM. Subcellular localization of (latent) transforming growth factor beta and the latent TGF-beta binding protein in rat hepatocytes and hepatic stellate cells. Hepatology. 1998;28:1588-1596. doi: 10.1002/hep.510280619.
36. Schon HT, Weiskirchen R. Immunomodulatory effects of transforming growth factor- in the liver. Hepatobiliary Surg Nutr. 2014;3:386-406. doi: 10.3978/j.issn.2304-3881.2014.11.06.
37. De Bleser PJ, Niki T, Rogiers V, Geerts A. Transforming growth factor-beta gene expression in normal and fibrotic rat liver. J Hepatol. 1997;26:886-893.
38. Nagy P, Schaff Z, Lapis K. Immunohistochemical detection of transforming growth factor-beta 1 in fibrotic liver diseases. Hepatology. 1991;14:269-273.
39. Castilla A, Prieto J, Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med. 1991;324:933-940. doi: 10.1056/NEJM199104043241401.
40. Shirai Y, Kawata S, Tamura S, Ito N, Tsushima H, Takaishi K, Kiso S, Matsuzawa Y. Plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma. Comparison with chronic liver diseases. Cancer. 1994;73:2275-2279.
41. Dooley S, ten Dijke P. TGF- in progression of liver disease. Cell Tissue Res. 2012;347:245-256. doi: 10.1007/s00441-011-1246-y.
42. Maganto-García E, Tarrio ML, Grabie N, Bu DX, Lichtman AH. Dynamic changes in regulatory T cells are linked to levels of diet-induced hypercholesterolemia. Circulation. 2011;124:185-195. doi: 10.1161/ CIRCULATIONAHA.110.006411.
43. Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, Merad M, Luedde T, Trautwein C, Tacke F. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology. 2009;50:261-274. doi: 10.1002/hep.22950.
44. Hammerich L, Heymann F, Tacke F. Role of IL-17 and Th17 cells in liver diseases. Clin Dev Immunol. 2011;2011:345803. doi: 10.1155/2011/345803.
45. Lan RY, Salunga TL, Tsuneyama K, Lian ZX, Yang GX, Hsu W, Moritoki Y, Ansari AA, Kemper C, Price J, Atkinson JP, Coppel RL, Gershwin ME. Hepatic IL-17 responses in human and murine primary biliary cirrhosis. J Autoimmun. 2009;32:43-51. doi: 10.1016/j.jaut.2008.11.001.
46. Lafdil F, Wang H, Park O, Zhang W, Moritoki Y, Yin S, Fu XY, Gershwin ME, Lian ZX, Gao B. Myeloid STAT3 inhibits T cell-mediated hepatitis by regulating T helper 1 cytokine and interleukin-17 production. Gastroenterology. 2009;137:2125-35.e1. doi: 10.1053/j. gastro.2009.08.004.
47. Taleb S, Romain M, Ramkhelawon B, Uyttenhove C, Pasterkamp G, Herbin O, Esposito B, Perez N, Yasukawa H, Van Snick J, Yoshimura A, Tedgui A, Mallat Z. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med. 2009;206:2067-2077. doi: 10.1084/jem.20090545.
48. Danzaki K, Matsui Y, Ikesue M, Ohta D, Ito K, Kanayama M, Kurotaki D, Morimoto J, Iwakura Y, Yagita H, Tsutsui H, Uede T. Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2012;32:273-280. doi: 10.1161/ATVBAHA.111.229997.
49. Butcher MJ, Filipowicz AR, Waseem TC, McGary CM, Crow KJ, Magilnick N, Boldin M, Lundberg PS, Galkina EV. Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFN+ Th1/Tregs. Circ Res. 2016;119:1190-1203. doi: 10.1161/ CIRCRESAHA.116.309764.
50. 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. doi: 10.1172/JCI119465.
51. GisterÅ A, Robertson AK, Andersson J, Ketelhuth DF, Ovchinnikova O, Nilsson SK, Lundberg AM, Li MO, Flavell RA, Hansson GK. Transforming growth factor- signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17-dependent pathway. Sci Transl Med. 2013;5:196ra100. doi: 10.1126/ scitranslmed.3006133.
52. Gao Q, Jiang Y, Ma T, Zhu F, Gao F, Zhang P, Guo C, Wang Q, Wang X, Ma C, Zhang Y, Chen W, Zhang L. A critical function of Th17 proinflammatory cells in the development of atherosclerotic plaque in mice. J Immunol. 2010;185:5820-5827. doi: 10.4049/jimmunol.1000116.
53. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, Rudensky AY. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451-455. doi: 10.1038/nature12726.
54. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496:518-522. doi: 10.1038/nature11868.
55. Forero-Peña DA, Gutierrez FR. Statins as modulators of regulatory T-cell biology. Mediators Inflamm. 2013;2013:167086. doi: 10.1155/2013/167086.
56. Kim YC, Kim KK, Shevach EM. Simvastatin induces Foxp3+ T regulatory cells by modulation of transforming growth factor-beta signal transduction. Immunology. 2010;130:484-493. doi: 10.1111/j.1365-2567.2010.03269.x.
57. Kagami S, Owada T, Kanari H, Saito Y, Suto A, Ikeda K, Hirose K, Watanabe N, Iwamoto I, Nakajima H. Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3+ regulatory T cells. Int Immunol. 2009;21:679-689. doi: 10.1093/intimm/dxp037.
58. Youssef S, Stüve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, Bravo M, Mitchell DJ, Sobel RA, Steinman L, Zamvil SS. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002;420:78-84. doi: 10.1038/nature01158.