Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: Pathology and beyond

World Journal of Hepatology

Volumn 7, Issue 15, 2015, Pages 1905-1912

  Vonghia, Luisa ^a,b   Francque, Sven ^a,b  

^a ANTWERP UNIVERSITY HOSPITAL   (Belgium)

^b UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Adipokines; Fibrosis; Immune system; Inflammation; Non alcoholic steatohepatitis

Indexed keywords

EID: 84938231078     PISSN: None     EISSN: 19485182     Source Type: Journal    
DOI: 10.4254/wjh.v7.i15.1905     Document Type: Editorial

References (64)

1. Masarone M, Federico A, Abenavoli L, Loguercio C, Persico M. Non alcoholic fatty liver: epidemiology and natural history. Rev Recent Clin Trials 2014; 9: 126-133 [PMID: 25514916 DOI: 10.2174/1574887109666141216111143]
2. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231 [PMID: 11961152 DOI: 10.1056/NEJMra011775]
3. Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 2013; 10: 330-344 [PMID: 23507799 DOI:10.1038/nrgastro.2013.41]
4. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 2005-2023 [PMID: 22488764 DOI: 10.1002/hep.25762]
5. Francque S, Laleman W, Verbeke L, Van Steenkiste C, Casteleyn C, Kwanten W, Van Dyck C, D'Hondt M, Ramon A, Vermeulen W, De Winter B, Van Marck E, Van Marck V, Pelckmans P, Michielsen P. Increased intrahepatic resistance in severe steatosis:endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture. Lab Invest 2012; 92: 1428-1439 [PMID:22890552 DOI: 10.1038/labinvest.2012.103]
6. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010; 52: 1836-1846 [PMID: 21038418 DOI: 10.1002/hep.24001]
7. Tran A, Gual P. Non-alcoholic steatohepatitis in morbidly obese patients. Clin Res Hepatol Gastroenterol 2013; 37: 17-29 [PMID:23347840 DOI: 10.1016/j.clinre.2012.07.005]
8. Maher JJ, Leon P, Ryan JC. Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis. Hepatology 2008; 48:670-678 [PMID: 18666225 DOI: 10.1002/hep.22399]
9. Kaminski DA, Randall TD. Adaptive immunity and adipose tissue biology. Trends Immunol 2010; 31: 384-390 [PMID: 20817556 DOI: 10.1016/j.it.2010.08.001]
10. Vonghia L, Michielsen P, Francque S. Immunological mechanisms in the pathophysiology of non-alcoholic steatohepatitis. Int J Mol Sci 2013; 14: 19867-19890 [PMID: 24084730 DOI: 10.3390/ ijms141019867]
11. Henning JR, Graffeo CS, Rehman A, Fallon NC, Zambirinis CP, Ochi A, Barilla R, Jamal M, Deutsch M, Greco S, Ego-Osuala M, Bin-Saeed U, Rao RS, Badar S, Quesada JP, Acehan D, Miller G. Dendritic cells limit fibroinflammatory injury in nonalcoholic1 Masarone M, Federico A, Abenavoli L, Loguercio C, Persico M. Non alcoholic fatty liver: epidemiology and natural history. Rev Recent Clin Trials 2014; 9: 126-133 [PMID: 25514916 DOI: 10.2174/1574887109666141216111143]
12. Winer S, Chan Y, Paltser G, Truong D, Tsui H, Bahrami J, Dorfman R, Wang Y, Zielenski J, Mastronardi F, Maezawa Y, Drucker DJ, Engleman E, Winer D, Dosch HM. Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 2009; 15: 921-929 [PMID: 19633657 DOI: 10.1038/nm.2001]
13. Ma X, Hua J, Mohamood AR, Hamad AR, Ravi R, Li Z. A highfat diet and regulatory T cells influence susceptibility to endotoxininduced liver injury. Hepatology 2007; 46: 1519-1529 [PMID:17661402 DOI: 10.1002/hep.21823]
14. Oo YH, Hubscher SG, Adams DH. Autoimmune hepatitis: new paradigms in the pathogenesis, diagnosis, and management.Hepatol Int 2010; 4: 475-493 [PMID: 20827405 DOI: 10.1007/ s12072-010-9183-5]
15. Söderberg C, Marmur J, Eckes K, Glaumann H, Sällberg M, Frelin L, Rosenberg P, Stål P, Hultcrantz R. Microvesicular fat, inter cellular adhesion molecule-1 and regulatory T-lymphocytes are of importance for the inflammatory process in livers with nonalcoholic steatohepatitis. APMIS 2011; 119: 412-420 [PMID:21635548 DOI: 10.1111/j.1600-0463.2011.02746.x]
16. Tang Y, Bian Z, Zhao L, Liu Y, Liang S, Wang Q, Han X, Peng Y, Chen X, Shen L, Qiu D, Li Z, Ma X. Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. Clin Exp Immunol 2011; 166: 281-290 [PMID: 21985374 DOI: 10.1111/j.1365-2249.2011.04471.x]
17. Polyzos SA, Kountouras J, Zavos C, Deretzi G. The potential adverse role of leptin resistance in nonalcoholic fatty liver disease:a hypothesis based on critical review of the literature. J Clin Gastroenterol 2011; 45: 50-54 [PMID: 20717042 DOI: 10.1097/M CG.0b013e3181ec5c66]
18. Yu Y, Liu Y, Shi FD, Zou H, Matarese G, La Cava A. Cutting edge:Leptin-induced RORγt expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J Immunol 2013; 190:3054-3058 [PMID: 23447682 DOI: 10.4049/jimmunol.1203275]
19. Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, Cong M, Iwaisako K, Liu X, Zhang M, Osterreicher CH, Stickel F, Ley K, Brenner DA, Kisseleva T. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 2012; 143: 765-766.e1-3[PMID: 22687286 DOI: 10.1053/j.gastro.2012.05.049]
20. Tajiri K, Shimizu Y, Tsuneyama K, Sugiyama T. Role of liverinfiltrating CD3+CD56+ natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2009; 21: 673-680 [PMID: 19318971 DOI: 10.1097/MEG.0b013e 32831bc3d6]
21. 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 [PMID: 10706553 DOI:10.1002/hep.510310313]
22. 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 [PMID: 16175608 DOI: 10.1002/ hep.20826]
23. Adler M, Taylor S, Okebugwu K, Yee H, Fielding C, Fielding G, Poles M. Intrahepatic natural killer T cell populations are increased in human hepatic steatosis. World J Gastroenterol 2011; 17:1725-1731 [PMID: 21483633 DOI: 10.3748/wjg.v17.i13.1725]
24. Syn WK, Agboola KM, Swiderska M, Michelotti GA, Liaskou E, Pang H, Xie G, Philips G, Chan IS, Karaca GF, Pereira Tde A, Chen Y, Mi Z, Kuo PC, Choi SS, Guy CD, Abdelmalek MF, Diehl AM. NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease. Gut 2012; 61: 1323-1329[PMID: 22427237 DOI: 10.1136/gutjnl-2011-301857]
25. Thomson AW, Knolle PA. Antigen-presenting cell function in the tolerogenic liver environment. Nat Rev Immunol 2010; 10: 753-766[PMID: 20972472 DOI: 10.1038/nri2858]
26. Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P. Interferon-gamma, a Th1 cytokine, regulates fatinflammation: a role for adaptive immunity in obesity. Circ Res 2008; 103: 467-476 [PMID: 18658050 DOI: 10.1161/CIRCRESA HA.108.177105]
27. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 2009; 15: 930-939[PMID: 19633656 DOI: 10.1038/nm.2002]
28. De Rosa V, Procaccini C, Calì G, Pirozzi G, Fontana S, Zappacosta S, La Cava A, Matarese G. A key role of leptin in the control of regulatory T cell proliferation. Immunity 2007; 26: 241-255 [PMID:17307705 DOI: 10.1016/j.immuni.2007.01.011]
29. Eller K, Kirsch A, Wolf AM, Sopper S, Tagwerker A, Stanzl U, Wolf D, Patsch W, Rosenkranz AR, Eller P. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 2011; 60: 2954-2962 [PMID:21911743 DOI: 10.2337/db11-0358]
30. Zeng C, Shi X, Zhang B, Liu H, Zhang L, Ding W, Zhao Y. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes:relationship with metabolic factors and complications. J Mol Med (Berl) 2012; 90: 175-186 [PMID: 21964948 DOI: 10.1007/ s00109-011-0816-5]
31. Zúñiga LA, Shen WJ, Joyce-Shaikh B, Pyatnova EA, Richards AG, Thom C, Andrade SM, Cua DJ, Kraemer FB, Butcher EC. IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol 2010; 185: 6947-6959 [PMID: 21037091 DOI: 10.4049/ jimmunol.1001269]
32. Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, Balk SP, O'Shea D, O'Farrelly C, Exley MA. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.Immunity 2012; 37: 574-587 [PMID: 22981538 DOI: 10.1016/j. immuni.2012.06.016]
33. Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, Blin-Wakkach C, Anty R, Iannelli A, Gugenheim J, Tran A, Bouloumié A, Gual P, Wakkach A. Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 2012; 61: 2238-2247 [PMID: 22596049 DOI:10.2337/db11-1274]
34. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 2011; 17: 610-617 [PMID: 21499269 DOI:10.1038/nm.2353]
35. Lumeng CN, Del Proposto JB, Westcott DJ, Saltiel AR. Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 2008; 57: 3239-3246 [PMID: 18829989 DOI: 10.2337/db08-0872]
36. Tsochatzis EA, Papatheodoridis GV, Archimandritis AJ. Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy. Mediators Inflamm 2009; 2009: 831670 [PMID: 19753129 DOI: 10.1155/2009/831670]
37. Gonciarz M, Bielański W, Partyka R, Brzozowski T, Konturek PC, Eszyk J, Celiński K, Reiter RJ, Konturek SJ. Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin. J Pineal Res 2013; 54: 154-161 [PMID: 22804755 DOI: 10.1111/j.1600-079X.2012.01023.x]
38. Kamada Y, Takehara T, Hayashi N. Adipocytokines and liver disease. J Gastroenterol 2008; 43: 811-822 [PMID: 19012034 DOI: 10.1007/s00535-008-2213-6]
39. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998; 394:897-901 [PMID: 9732873 DOI: 10.1038/29795]
40. Procaccini C, Jirillo E, Matarese G. Leptin as an immunomodulator.Mol Aspects Med 2012; 33: 35-45 [PMID: 22040697 DOI: 10.1016/ j.mam.2011.10.012]
41. Matsumoto H, Tamura S, Kamada Y, Kiso S, Fukushima J, Wada A, Maeda N, Kihara S, Funahashi T, Matsuzawa Y, Shimomura I, Hayashi N. Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice.World J Gastroenterol 2006; 12: 3352-3358 [PMID: 16733851]
42. 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 [PMID: 10961870]
43. Marchesini G, Pagotto U, Bugianesi E, De Iasio R, Manini R, Vanni E, Pasquali R, Melchionda N, Rizzetto M. Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance. J Clin Endocrinol Metab 2003; 88: 5674-5679[PMID: 14671152 DOI: 10.1210/jc.2003-031094]
44. Pagano C, Soardo G, Pilon C, Milocco C, Basan L, Milan G, Donnini D, Faggian D, Mussap M, Plebani M, Avellini C, Federspil G, Sechi LA, Vettor R. Increased serum resistin in nonalcoholic fatty liver disease is related to liver disease severity and not to insulin resistance. J Clin Endocrinol Metab 2006; 91: 1081-1086[PMID: 16394091 DOI: 10.1210/jc.2005-1056]
45. El-Assal O, Hong F, Kim WH, Radaeva S, Gao B. IL-6-deficient mice are susceptible to ethanol-induced hepatic steatosis: IL-6 protects against ethanol-induced oxidative stress and mitochondrial permeability transition in the liver. Cell Mol Immunol 2004; 1:205-211 [PMID: 16219169]
46. Hardy T, Anstee QM, Day CP. Nonalcoholic fatty liver disease:new treatments. Curr Opin Gastroenterol 2015; 31: 175-183[PMID: 25774446 DOI: 10.1097/MOG.0000000000000175]
47. Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, Balas B, Gastaldelli A, Tio F, Pulcini J, Berria R, Ma JZ, Dwivedi S, Havranek R, Fincke C, De Fronzo R, Bannayan GA, Schenker S, Cusi K. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297-2307[PMID: 17135584 DOI: 10.1056/NEJMoa060326]
48. Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, Yamaguchi M, Tanabe H, Kimura-Someya T, Shirouzu M, Ogata H, Tokuyama K, Ueki K, Nagano T, Tanaka A, Yokoyama S, Kadowaki T. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 2013; 503: 493-499[PMID: 24172895 DOI: 10.1038/nature12656]
49. von Boehmer H, Daniel C. Therapeutic opportunities for manipulating T(Reg) cells in autoimmunity and cancer. Nat Rev Drug Discov 2013; 12: 51-63 [PMID: 23274471 DOI: 10.1038/ nrd3683]
50. Ilan Y, Maron R, Tukpah AM, Maioli TU, Murugaiyan G, Yang K, Wu HY, Weiner HL. Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. Proc Natl Acad Sci USA 2010; 107: 9765-9770 [PMID:20445103 DOI: 10.1073/pnas.0908771107]
51. da Cunha AP, Weiner HL. Induction of immunological tolerance by oral anti-CD3. Clin Dev Immunol 2012; 2012: 425021 [PMID:22162715 DOI: 10.1155/2012/425021]
52. Mizrahi M, Shabat Y, Ben Ya'acov A, Lalazar G, Adar T, Wong V, Muller B, Rawlin G, Ilan Y. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH. J Inflamm Res 2012; 5: 141-150 [PMID: 23293533 DOI: 10.2147/ JIR.S35227]
53. Shabat Y, Lichtenstein Y, Zolotarov L, Ben Ya'acov A, Ilan Y. Hepatoprotective effect of DT56a is associated with changes in natural killer T cells and regulatory T cells. J Dig Dis 2013; 14:84-92 [PMID: 23134214 DOI: 10.1111/1751-2980.12003]
54. Roncarolo MG, Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat Rev Immunol 2007; 7: 585-598 [PMID: 17653126 DOI: 10.1038/ nri2138]
55. Cipolletta D, Kolodin D, Benoist C, Mathis D. Tissular T(regs): a unique population of adipose-tissue-resident Foxp3+CD4+ T cells that impacts organismal metabolism. Semin Immunol 2011; 23:431-437 [PMID: 21724410 DOI: 10.1016/j.smim.2011.06.002]
56. Lau P, Fitzsimmons RL, Pearen MA, Watt MJ, Muscat GE. Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle.Diabetologia 2011; 54: 1169-1180 [PMID: 21279323 DOI: 10.1007/ s00125-011-2046-3]
57. Hoffstedt J, Arner E, Wahrenberg H, Andersson DP, Qvisth V, Löfgren P, Rydén M, Thörne A, Wirén M, Palmér M, Thorell A, Toft E, Arner P. Regional impact of adipose tissue morphology on the metabolic profile in morbid obesity. Diabetologia 2010; 53:2496-2503 [PMID: 20830466 DOI: 10.1007/s00125-010-1889-3]
58. Sin TK, Yung BY, Siu PM. Modulation of SIRT1-Foxo1 signaling axis by resveratrol: implications in skeletal muscle aging and insulin resistance. Cell Physiol Biochem 2015; 35: 541-552 [PMID:25612477 DOI: 10.1159/000369718]
59. Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, Shu F, Gao Y, Yuan L, Zhang Q, Mi M. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig Liver Dis 2015; 47: 226-232 [PMID: 25577300 DOI: 10.1016/j.dld.2014.11.015]
60. Friedman SL. Significant Anti-Fibrotic Activity of Cenicriviroc, A Dual CCR2/CCR5 Antagonist, in a Rat Model of Thioac- etamide-Induced Liver Fibrosis and Cirrhosis. Hepatology 2013; 58:1381A-1382A
61. Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY. Performance of the aspartate aminotransferase-toplatelet ratio index for the staging of hepatitis C-related fibrosis:an updated meta-analysis. Hepatology 2011; 53: 726-736 [PMID:21319189 DOI: 10.1002/hep.24105]
62. Thompson M, Chang W, Jenkins H, Flynt A, Gottwald M, Lefebvre E. Improvements in APRI and FIB-4 fibrosis scores correlate with decreases in sCD14 in HIV-1 infected adults receiving cenicriviroc over 48 weeks. Hepatology 2014; 60: 424A
63. Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 2006; 43: 1317-1325 [PMID: 16729309 DOI: 10.1002/hep.21178]
64. Weston CJ, Shepherd EL, Claridge LC, Rantakari P, Curbishley SM, Tomlinson JW, Hubscher SG, Reynolds GM, Aalto K, Anstee QM, Jalkanen S, Salmi M, Smith DJ, Day CP, Adams DH. Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis. J Clin Invest 2015; 125: 501-520 [PMID: 25562318 DOI:10.1172/JCI73722]