Fat: A matter of disturbance for the immune system

World Journal of Gastroenterology

Volumn 16, Issue 38, 2010, Pages 4762-4772

  Federico, Alessandro ^a   D'Aiuto, Elena ^a   Borriello, Francesco ^a   Barra, Giusi ^a   Gravina, Antonietta Gerarda ^a   Romano, Marco ^a   de Palma, Raffaele ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

Adipocytokine; Adipose tissue; Fat; Immune system; Kupffer cell; Natural killer; Steatosis

Indexed keywords

ADIPOCYTOKINE; CYTOKINE; FAT;

ADIPOCYTE; ARTICLE; ATHEROSCLEROSIS; AUTOIMMUNE DISEASE; CHRONIC LIVER DISEASE; DISEASE COURSE; FATTY LIVER; GASTROINTESTINAL DISEASE; HUMAN; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOREGULATION; INFLAMMATORY DISEASE; INNATE IMMUNITY; KUPFFER CELL; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MACROPHAGE; MALNUTRITION; NEOPLASM; NONALCOHOLIC FATTY LIVER; OBESITY; OVERNUTRITION; WHITE ADIPOSE TISSUE;

EID: 78049507979     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v16.i38.4762     Document Type: Article

References (105)

1. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005; 115: 1111-1119
2. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004; 4: 579-591
3. Mannino DM, Mott J, Ferdinands JM, Camargo CA, Friedman M, Greves HM, Redd SC. Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY). Int J Obes (Lond) 2006; 30: 6-13
4. Ogden CL, Carroll MD, McDowell MA, Flegal KM. Obesity among adults in the United States--no statistically significant chance since 2003-2004. NCHS Data Brief 2007; 1-8
5. Ogden CL, Carroll MD, Flegal KM. High body mass index for age among US children and adolescents, 2003-2006. JAMA 2008; 299: 2401-2405
6. Berghöfer A, Pischon T, Reinhold T, Apovian CM, Sharma AM, Willich SN. Obesity prevalence from a European perspective: a systematic review. BMC Public Health 2008; 8: 200
7. Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, Kahn R. Waist circumference and cardiometabolic risk: a consensus statement from shaping America's health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care 2007; 30: 1647-1652
8. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96: 939-949
9. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006; 6: 772-783
10. Gil A, María Aguilera C, Gil-Campos M, Cañete R. Altered signalling and gene expression associated with the immune system and the inflammatory response in obesity. Br J Nutr 2007; 98 Suppl 1: S121-S126
11. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006; 17: 4-12
12. Mendall MA, Patel P, Asante M, Ballam L, Morris J, Strachan DP, Camm AJ, Northfield TC. Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. Heart 1997; 78: 273-277
13. Tataranni PA, Ortega E. A burning question: does an adipokine- induced activation of the immune system mediate the effect of overnutrition on type 2 diabetes? Diabetes 2005; 54: 917-927
14. Nieman DC, Henson DA, Nehlsen-Cannarella SL, Ekkens M, Utter AC, Butterworth DE, Fagoaga OR. Influence of obesity on immune function. J Am Diet Assoc 1999; 99: 294-299
15. Ghanim H, Aljada A, Hofmeyer D, Syed T, Mohanty P, Dandona P. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004; 110: 1564-1571
16. Björkbacka H, Kunjathoor VV, Moore KJ, Koehn S, Ordija CM, Lee MA, Means T, Halmen K, Luster AD, Golenbock DT, Freeman MW. Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nat Med 2004; 10: 416-421
17. Maher JJ, Leon P, Ryan JC. Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis. Hepatology 2008; 48: 670-678
18. Szabo G, Mandrekar P, Dolganiuc A. Innate immune response and hepatic inflammation. Semin Liver Dis 2007; 27: 339-350
19. Sahai A, Malladi P, Pan X, Paul R, Melin-Aldana H, Green RM, Whitington PF. Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin. Am J Physiol Gastrointest Liver Physiol 2004; 287: G1035-G1043
20. Kojima H, Sakurai S, Uemura M, Takekawa T, Morimoto H, Tamagawa Y, Fukui H. Difference and similarity between non-alcoholic steatohepatitis and alcoholic liver disease. Alcohol Clin Exp Res 2005; 29: 259S-263S
21. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006; 43: S99-S112
22. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006; 40 Suppl 1: S5-S10
23. Day CP. From fat to inflammation. Gastroenterology 2006; 130: 207-210
24. Lieber CS. Alcoholic liver disease: new insights in pathogenesis lead to new treatments. J Hepatol 2000; 32: 113-128
25. Cheung O, Sanyal AJ. Hepatitis C infection and nonalcoholic fatty liver disease. Clin Liver Dis 2008; 12: 573-585, viii-ix
26. Molina PE, McClain C, Valla D, Guidot D, Diehl AM, Lang CH, Neuman M. Molecular pathology and clinical aspects of alcohol-induced tissue injury. Alcohol Clin Exp Res 2002; 26: 120-128
27. Lumeng L, Crabb DW. Genetic aspects and risk factors in alcoholism and alcoholic liver disease. Gastroenterology 1994; 107: 572-578
28. Harrison SA, Diehl AM. Fat and the liver--a molecular overview. Semin Gastrointest Dis 2002; 13: 3-16
29. Yang S, Lin H, Diehl AM. Fatty liver vulnerability to endotoxin- induced damage despite NF-kappaB induction and inhibited caspase 3 activation. Am J Physiol Gastrointest Liver Physiol 2001; 281: G382-G392
30. Day CP. Natural history of NAFLD: remarkably benign in the absence of cirrhosis. Gastroenterology 2005; 129: 375-378
31. Ioannou GN. Implications of elevated serum alanine aminotransferase levels: think outside the liver. Gastroenterology 2008; 135: 1851-1854
32. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 2002; 36: 1349-1354
33. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome--a new worldwide definition. Lancet 2005; 366: 1059-1062
34. Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, Kahn R. Waist circumference and cardiometabolic risk: a consensus statement from shaping America's health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care 2007; 30: 1647-1652
35. Zimmet P, Magliano D, Matsuzawa Y, Alberti G, Shaw J. The metabolic syndrome: a global public health problem and a new definition. J Atheroscler Thromb 2005; 12: 295-300
36. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006; 116: 1784-1792
37. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000; 96: 1723-1732
38. Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun 2004; 316: 924-929
39. Park PH, Huang H, McMullen MR, Mandal P, Sun L, Nagy LE. Suppression of lipopolysaccharide-stimulated tumor necrosis factor-alpha production by adiponectin is mediated by transcriptional and post-transcriptional mechanisms. J Biol Chem 2008; 283: 26850-26858
40. Thakur V, Pritchard MT, McMullen MR, Nagy LE. Adiponectin normalizes LPS-stimulated TNF-alpha production by rat Kupffer cells after chronic ethanol feeding. Am J Physiol Gastrointest Liver Physiol 2006; 290: G998-G1007
41. Huang H, Park PH, McMullen MR, Nagy LE. Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. J Gastroenterol Hepatol 2008; 23 Suppl 1: S50-S53
42. Kuga S, Otsuka T, Niiro H, Nunoi H, Nemoto Y, Nakano T, Ogo T, Umei T, Niho Y. Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase. Exp Hematol 1996; 24: 151-157
43. Kolak M, Westerbacka J, Velagapudi VR, Wågsäter D, Yetukuri L, Makkonen J, Rissanen A, Häkkinen AM, Lindell M, Bergholm R, Hamsten A, Eriksson P, Fisher RM, Oresic M, Yki-Järvinen H. Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes 2007; 56: 1960-1968
44. La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol 2004; 4: 371-379
45. Angulo P, Alba LM, Petrovic LM, Adams LA, Lindor KD, Jensen MD. Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. J Hepatol 2004; 41: 943-949
46. Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 2003; 108: 736-740
47. Haydon G, Lalor PF, Hubscher SG, Adams DH. Lymphocyte recruitment to the liver in alcoholic liver disease. Alcohol 2002; 27: 29-36
48. Burra P, Hubscher SG, Shaw J, Elias E, Adams DH. Is the intercellular adhesion molecule-1/leukocyte function associ-ated antigen 1 pathway of leukocyte adhesion involved in the tissue damage of alcoholic hepatitis? Gut 1992; 33: 268-271
49. Kurkijärvi R, Yegutkin GG, Gunson BK, Jalkanen S, Salmi M, Adams DH. Circulating soluble vascular adhesion protein 1 accounts for the increased serum monoamine oxidase activity in chronic liver disease. Gastroenterology 2000; 119: 1096-103
50. Adams DH, Burra P, Hubscher SG, Elias E, Newman W. Endothelial activation and circulating vascular adhesion molecules in alcoholic liver disease. Hepatology 1994; 19: 588-594
51. Kurkijärvi R, Adams DH, Leino R, Möttönen T, Jalkanen S, Salmi M. Circulating form of human vascular adhesion protein- 1 (VAP-1): increased serum levels in inflammatory liver diseases. J Immunol 1998; 161: 1549-1557
52. Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 1994; 14: 1431-1437
53. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005; 307: 426-430
54. Revollo JR, Körner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007; 6: 363-375
55. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 2007; 178: 1748-1758
56. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540-543
57. Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci USA 1997; 94: 2557-2562
58. Guebre-Xabier M, Yang S, Lin HZ, Schwenk R, Krzych U, Diehl AM. Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage. Hepatology 2000; 31: 633-640
59. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L. NKT cells: what's in a name? Nat Rev Immunol 2004; 4: 231-237
60. Godfrey DI, Kronenberg M. Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 2004; 114: 1379-1388
61. Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol 2005; 174: 3137-3142
62. 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
63. Black BL, Croom J, Eisen EJ, Petro AE, Edwards CL, Surwit RS. Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice. Metabolism 1998; 47: 1354-1359
64. Klugewitz K, Adams DH, Emoto M, Eulenburg K, Hamann A. The composition of intrahepatic lymphocytes: shaped by selective recruitment? Trends Immunol 2004; 25: 590-594
65. Johnston B, Kim CH, Soler D, Emoto M, Butcher EC. Differential chemokine responses and homing patterns of murine TCR alpha beta NKT cell subsets. J Immunol 2003; 171: 2960-2969
66. Seino K, Harada M, Taniguchi M. NKT cells are relatively resistant to apoptosis. Trends Immunol 2004; 25: 219-221
67. Li Z, Lin H, Yang S, Diehl AM. Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system. Gastroenterology 2002; 123: 1304-1310
68. Schmieg J, Yang G, Franck RW, Van Rooijen N, Tsuji M. Glycolipid presentation to natural killer T cells differs in an organ-dependent fashion. Proc Natl Acad Sci USA 2005; 102: 1127-1132
69. Kremer M, Thomas E, Milton RJ, Perry AW, van Rooijen N, Wheeler MD, Zacks S, Fried M, Rippe RA, Hines IN. Kupffer cell and interleukin-12-dependent loss of natural killer T cells in hepatosteatosis. Hepatology 2010; 51: 130-141
70. Trembleau S, Germann T, Gately MK, Adorini L. The role of IL-12 in the induction of organ-specific autoimmune diseases. Immunol Today 1995; 16: 383-386
71. Adams LA, Lindor KD, Angulo P. The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic Fatty liver disease. Am J Gastroenterol 2004; 99: 1316-1320
72. Brozovic S, Nagaishi T, Yoshida M, Betz S, Salas A, Chen D, Kaser A, Glickman J, Kuo T, Little A, Morrison J, Corazza N, Kim JY, Colgan SP, Young SG, Exley M, Blumberg RS. CD1d function is regulated by microsomal triglyceride transfer protein. Nat Med 2004; 10: 535-539
73. Namikawa C, Shu-Ping Z, Vyselaar JR, Nozaki Y, Nemoto Y, Ono M, Akisawa N, Saibara T, Hiroi M, Enzan H, Onishi S. Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in nonalcoholic steatohepatitis. J Hepatol 2004; 40: 781-786
74. Hua J, Ma X, Webb T, Potter JJ, Oelke M, Li Z. Dietary fatty acids modulate antigen presentation to hepatic NKT cells in nonalcoholic fatty liver disease. J Lipid Res 2010; 51: 1696-1703
75. Billerbeck E, Kang YH, Walker L, Lockstone H, Grafmueller S, Fleming V, Flint J, Willberg CB, Bengsch B, Seigel B, Ramamurthy N, Zitzmann N, Barnes EJ, Thevanayagam J, Bhagwanani A, Leslie A, Oo YH, Kollnberger S, Bowness P, Drognitz O, Adams DH, Blum HE, Thimme R, Klenerman P. Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA 2010; 107: 3006-3011
76. Cosmi L, De Palma R, Santarlasci V, Maggi L, Capone M, Frosali F, Rodolico G, Querci V, Abbate G, Angeli R, Berrino L, Fambrini M, Caproni M, Tonelli F, Lazzeri E, Parronchi P, Liotta F, Maggi E, Romagnani S, Annunziato F. Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. J Exp Med 2008; 205: 1903-1916
77. Yang L, Zhang Y, Wang L, Fan F, Zhu L, Li Z, Ruan X, Huang H, Wang Z, Huang Z, Huang Y, Yan X, Chen Y. Amelioration of high fat diet induced liver lipogenesis and hepatic steatosis by interleukin-22. J Hepatol 2010; 53: 339-347
78. Elizondo A, Araya J, Rodrigo R, Poniachik J, Csendes A, Maluenda F, Díaz JC, Signorini C, Sgherri C, Comporti M, Videla LA. Polyunsaturated fatty acid pattern in liver and erythrocyte phospholipids from obese patients. Obesity (Silver Spring) 2007; 15: 24-31
79. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37: 1202-1219
80. Farrell GC, Teoh NC, McCuskey RS. Hepatic microcirculation in fatty liver disease. Anat Rec (Hoboken) 2008; 291: 684-692
81. Kim JK. Fat uses a TOLL-road to connect inflammation and diabetes. Cell Metab 2006; 4: 417-419
82. Lee JY, Hwang DH. The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Mol Cells 2006; 21: 174-185
83. Marí M, Caballero F, Colell A, Morales A, Caballeria J, Fernandez A, Enrich C, Fernandez-Checa JC, García-Ruiz C. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab 2006; 4: 185-198
84. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006; 116: 3015-3025
85. Lee JY, Ye J, Gao Z, Youn HS, Lee WH, Zhao L, Sizemore N, Hwang DH. Reciprocal modulation of Toll-like receptor-4 signaling pathways involving MyD88 and phosphatidylinositol 3-kinase/AKT by saturated and polyunsaturated fatty acids. J Biol Chem 2003; 278: 37041-37051
86. Wouters K, van Gorp PJ, Bieghs V, Gijbels MJ, Duimel H, Lütjohann D, Kerksiek A, van Kruchten R, Maeda N, Staels B, van Bilsen M, Shiri-Sverdlov R, Hofker MH. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis. Hepatology 2008; 48: 474-486
87. Shiri-Sverdlov R, Wouters K, van Gorp PJ, Gijbels MJ, Noel B, Buffat L, Staels B, Maeda N, van Bilsen M, Hofker MH. Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates. J Hepatol 2006; 44: 732-741
88. Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23-35
89. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM. The nuclear receptor superfamily: the second decade. Cell 1995; 83: 835-839
90. Sugden MC, Holness MJ. Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance. Biochem Soc Trans 2008; 36: 891-900
91. Younossi ZM. Review article: current management of nonalcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2008; 28: 2-12
92. Rigamonti E, Chinetti-Gbaguidi G, Staels B. Regulation of macrophage functions by PPAR-alpha, PPAR-gamma, and LXRs in mice and men. Arterioscler Thromb Vasc Biol 2008; 28: 1050-1059
93. Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A. Oxidative metabolism and PGC-1beta attenuate macrophagemediated inflammation. Cell Metab 2006; 4: 13-24
94. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 2007; 447: 1116-1120
95. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 2008; 7: 496-507
96. Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH. Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 2008; 7: 485-495
97. Omenetti A, Diehl AM. The adventures of sonic hedgehog in development and repair. II. Sonic hedgehog and liver development, inflammation, and cancer. Am J Physiol Gastrointest Liver Physiol 2008; 294: G595-G598
98. Jung Y, Witek RP, Syn WK, Choi SS, Omenetti A, Premont R, Guy CD, Diehl AM. Signals from dying hepatocytes trigger growth of liver progenitors. Gut 2010; 59: 655-665
99. Syn WK, Witek RP, Curbishley SM, Jung Y, Choi SS, Enrich B, Omenetti A, Agboola KM, Fearing CM, Tilg H, Adams DH, Diehl AM. Role for hedgehog pathway in regulating growth and function of invariant NKT cells. Eur J Immunol 2009; 39: 1879-1892
100. Syn WK, Oo YH, Pereira TA, Karaca GF, Jung Y, Omenetti A, Witek RP, Choi SS, Guy CD, Fearing CM, Teaberry V, Pereira FE, Adams DH, Diehl AM. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 2010; 51: 1998-2007
101. Reiman RM, Thompson RW, Feng CG, Hari D, Knight R, Cheever AW, Rosenberg HF, Wynn TA. Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity. Infect Immun 2006; 74: 1471-1479
102. Delano MJ, Scumpia PO, Weinstein JS, Coco D, Nagaraj S, Kelly-Scumpia KM, O'Malley KA, Wynn JL, Antonenko S, Al-Quran SZ, Swan R, Chung CS, Atkinson MA, Ramphal R, Gabrilovich DI, Reeves WH, Ayala A, Phillips J, Laface D, Heyworth PG, Clare-Salzler M, Moldawer LL. MyD88- dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med 2007; 204: 1463-1474
103. Deng ZB, Liu Y, Liu C, Xiang X, Wang J, Cheng Z, Shah SV, Zhang S, Zhang L, Zhuang X, Michalek S, Grizzle WE, Zhang HG. Immature myeloid cells induced by a high-fat diet contribute to liver inflammation. Hepatology 2009; 50: 1412-1420
104. van der Poorten D, Milner KL, Hui J, Hodge A, Trenell MI, Kench JG, London R, Peduto T, Chisholm DJ, George J. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology 2008; 48: 449-457
105. Yu S, Liu C, Su K, Wang J, Liu Y, Zhang L, Li C, Cong Y, Kimberly R, Grizzle WE, Falkson C, Zhang HG. Tumor exosomes inhibit differentiation of bone marrow dendritic cells. J Immunol 2007; 178: 6867-6875