Immune cells and metabolism

Handbook of Experimental Pharmacology

Volumn 233, Issue , 2015, Pages 221-249

  Chatzigeorgiou, Antonios ^a,b   Chavakis, Triantafyllos ^a,b  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b GERMAN CENTER FOR DIABETES RESEARCH DZD   (Germany)

Author keywords

Adipose tissue; Inflammation; Insulin resistance; Liver; Lymphocytes; Macrophages; Non alcoholic steatohepatitis (NASH); T regulatory cells

Indexed keywords

CYTOKINE;

ADAPTIVE IMMUNITY; ADIPOCYTE; ADIPOGENESIS; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; EOSINOPHIL; HOMEOSTASIS; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; INNATE IMMUNITY; INSULIN RESISTANCE; LIVER CELL; MACROPHAGE; MAST CELL; METABOLIC DISORDER; NATURAL KILLER T CELL; NEUTROPHIL; NONHUMAN; OBESITY; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; ADIPOSE TISSUE; ANIMAL; IMMUNOLOGY; LIVER; METABOLIC DISEASES; METABOLISM; PHYSIOLOGY; T LYMPHOCYTE;

ADAPTIVE IMMUNITY; ADIPOSE TISSUE; ANIMALS; HUMANS; IMMUNITY, INNATE; INFLAMMATION; LIVER; MACROPHAGES; METABOLIC DISEASES; OBESITY; T-LYMPHOCYTES;

EID: 84961612924     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/164_2015_8     Document Type: Article

References (213)

1. Adler M, Taylor S, Okebugwu K, Yee H, Fielding C, Fielding G, Poles M (2011) Intrahepatic natural killer T cell populations are increased in human hepatic steatosis. World J Gastroenterol 17:1725-1731
2. Altintas MM, Azad A, Nayer B, Contreras G, Zaias J, Faul C, Reiser J, Nayer A (2011a) Mast cells, macrophages, and crown-like structures distinguish subcutaneous from visceral fat in mice. J Lipid Res 52:480-488
3. Altintas MM, Rossetti MA, Nayer B, Puig A, Zagallo P, Ortega LM, Johnson KB, McNamara G, Reiser J, Mendez AJ, Nayer A (2011b) Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice. Lipids Health Dis 10:198
4. Altintas MM, Nayer B, Walford EC, Johnson KB, Gaidosh G, Reiser J, De La Cruz-Munoz N, Ortega LM, Nayer A (2012) Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice. Lipids Health Dis 11:21
5. Annunziato F, Romagnani C, Romagnani S (2014) The 3 major types of innate and adaptive cellmediated effector immunity. J Allergy Clin Immunol 135:626-635
6. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11:191-198
7. Bai Y, Sun Q (2015) Macrophage recruitment in obese adipose tissue. Obes Rev 16:127-136
8. Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, Blin-Wakkach C, Anty R, Iannelli A, Gugenheim J, Tran A, Bouloumie A, Gual P, Wakkach A (2012) Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61:2238-2247
9. Bieghs V, Walenbergh SM, Hendrikx T, van Gorp PJ, Verheyen F, Olde Damink SW, Masclee AA, Koek GH, Hofker MH, Binder CJ, Shiri-Sverdlov R (2013) Trapping of oxidized LDL in lysosomes of Kupffer cells is a trigger for hepatic inflammation. Liver Int 33:1056-1061
10. Borg NA, Wun KS, Kjer-Nielsen L, Wilce MC, Pellicci DG, Koh R, Besra GS, Bharadwaj M, Godfrey DI, McCluskey J, Rossjohn J (2007) CD1d-lipid-antigen recognition by the semiinvariant NKT T-cell receptor. Nature 448:44-49
11. Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, Thome JJ, Farber DL, Lutfy K, Seale P, Artis D (2014) Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 519:242-246
12. Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T (2012) Lymphocytes in obesity-related adipose tissue inflammation. Diabetologia 55:2583-2592
13. Chatzigeorgiou A, Chung KJ, Garcia-Martin R, Alexaki VI, Klotzsche-von Ameln A, Phieler J, Sprott D, Kanczkowski W, Tzanavari T, Bdeir M, Bergmann S, Cartellieri M, Bachmann M, Nikolakopoulou P, Androutsellis-Theotokis A, Siegert G, Bornstein SR, Muders MH, Boon L, Karalis KP, Lutgens E, Chavakis T (2014a) Dual role of B7 costimulation in obesity-related nonalcoholic steatohepatitis and metabolic dysregulation. Hepatology 60:1196-1210
14. Chatzigeorgiou A, Seijkens T, Zarzycka B, Engel D, Poggi M, van den Berg S, van den Berg S, Soehnlein O, Winkels H, Beckers L, Lievens D, Driessen A, Kusters P, Biessen E, Garcia-Martin R, Klotzsche-von Ameln A, Gijbels M, Noelle R, Boon L, Hackeng T, Schulte KM, Xu A, Vriend G, Nabuurs S, Chung KJ, Willems van Dijk K, Rensen PC, Gerdes N, de Winther M, Block NL, Schally AV, Weber C, Bornstein SR, Nicolaes G, Chavakis T, Lutgens E (2014b) Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance. Proc Natl Acad Sci U S A 111:2686-2691
15. Chawla A, Nguyen KD, Goh YP (2011) Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 11:738-749
16. Chen X, Wu Y, Wang L (2013) Fat-resident Tregs: an emerging guard protecting from obesityassociated metabolic disorders. Obes Rev 14:568-578
17. Chen Y, Tian J, Tian X, Tang X, Rui K, Tong J, Lu L, Xu H, Wang S (2014) Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS One 9: e92450
18. Chmelar J, Chung KJ, Chavakis T (2013) The role of innate immune cells in obese adipose tissue inflammation and development of insulin resistance. Thromb Haemost 109:399-406
19. Cho KW, Morris DL, DelProposto JL, Geletka L, Zamarron B, Martinez-Santibanez G, Meyer KA, Singer K, O’Rourke RW, Lumeng CN (2014) An MHC II-dependent activation loop between adipose tissue macrophages and CD4+ T cells controls obesity-induced inflammation. Cell Rep 9:605-617
20. Cildir G, Akincilar SC, Tergaonkar V (2014) Chronic adipose tissue inflammation: all immune cells on the stage. Trends Mol Med 19:487-500
21. Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, Benoist C, Mathis D (2012) PPARgamma is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486:549-553
22. Cipolletta D, Cohen P, Spiegelman BM, Benoist C, Mathis D (2015) Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARgamma effects. Proc Natl Acad Sci U S A 112:482-487
23. Cohen JC, Horton JD, Hobbs HH (2011) Human fatty liver disease: old questions and new insights. Science 332:1519-1523
24. Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10:479-489
25. De Rosa V, Procaccini C, Cali G, Pirozzi G, Fontana S, Zappacosta S, La Cava A, Matarese G (2007) A key role of leptin in the control of regulatory T cell proliferation. Immunity 26:241-255
26. De Taeye BM, Novitskaya T, McGuinness OP, Gleaves L, Medda M, Covington JW, Vaughan DE (2007) Macrophage TNF-alpha contributes to insulin resistance and hepatic steatosis in dietinduced obesity. Am J Physiol Endocrinol Metab 293:E713-E725
27. DeFuria J, Belkina AC, Jagannathan-Bogdan M, Snyder-Cappione J, Carr JD, Nersesova YR, Markham D, Strissel KJ, Watkins AA, Zhu M, Allen J, Bouchard J, Toraldo G, Jasuja R, Obin MS, McDonnell ME, Apovian C, Denis GV, Nikolajczyk BS (2013) B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci U S A 110:5133-5138
28. Deiuliis J, Shah Z, Shah N, Needleman B, Mikami D, Narula V, Perry K, Hazey J, Kampfrath T, Kollengode M, Sun Q, Satoskar AR, Lumeng C, Moffatt-Bruce S, Rajagopalan S (2011) Visceral adipose inflammation in obesity is associated with critical alterations in t regulatory cell numbers. PLoS One 6:e16376
29. Drechsler M, Megens RT, van Zandvoort M, Weber C, Soehnlein O (2010) Hyperlipidemiatriggered neutrophilia promotes early atherosclerosis. Circulation 122:1837-1845
30. Duffaut C, Galitzky J, Lafontan M, Bouloumie A (2009a) Unexpected trafficking of immune cells within the adipose tissue during the onset of obesity. Biochem Biophys Res Commun 384:482-485
31. Duffaut C, Zakaroff-Girard A, Bourlier V, Decaunes P, Maumus M, Chiotasso P, Sengenes C, Lafontan M, Galitzky J, Bouloumie A (2009b) Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. Arterioscler Thromb Vasc Biol 29:1608-1614
32. Eguchi K, Manabe I (2013) Macrophages and islet inflammation in type 2 diabetes. Diabetes Obes Metab 15(Suppl 3):152-158
33. Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R (2012) Saturated fatty acid and TLR signaling link beta cell dysfunction and islet inflammation. Cell Metab 15:518-533
34. Ehses JA, Perren A, Eppler E, Ribaux P, Pospisilik JA, Maor-Cahn R, Gueripel X, Ellingsgaard H, Schneider MK, Biollaz G, Fontana A, Reinecke M, Homo-Delarche F, Donath MY (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356-2370
35. Elgazar-Carmon V, Rudich A, Hadad N, Levy R (2008) Neutrophils transiently infiltrate intraabdominal fat early in the course of high-fat feeding. J Lipid Res 49:1894-1903
36. Elinav E, Pappo O, Sklair-Levy M, Margalit M, Shibolet O, Gomori M, Alper R, Thalenfeld B, Engelhardt D, Rabbani E, Ilan Y (2006) Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping. J Pathol 209:121-128
37. Ericksen RE, Rose S, Westphalen CB, Shibata W, Muthupalani S, Tailor Y, Friedman RA, Han W, Fox JG, Ferrante AW Jr, Wang TC (2014) Obesity accelerates Helicobacter felis-induced gastric carcinogenesis by enhancing immature myeloid cell trafficking and TH17 response. Gut 63:385-394
38. Eskan MA, Jotwani R, Abe T, Chmelar J, Lim JH, Liang S, Ciero PA, Krauss JL, Li F, Rauner M, Hofbauer LC, Choi EY, Chung KJ, Hashim A, Curtis MA, Chavakis T, Hajishengallis G (2012) The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat Immunol 13:465-473
39. Fabbrini E, Cella M, McCartney SA, Fuchs A, Abumrad NA, Pietka TA, Chen Z, Finck BN, Han DH, Magkos F, Conte C, Bradley D, Fraterrigo G, Eagon JC, Patterson BW, Colonna M, Klein S (2013) Association between specific adipose tissue CD4+ T-cell populations and insulin resistance in obese individuals. Gastroenterology 145:366-74.e1-3
40. Fabrizi M, Marchetti V, Mavilio M, Marino A, Casagrande V, Cavalera M, Moreno-Navarrete JM, Mezza T, Sorice GP, Fiorentino L, Menghini R, Lauro R, Monteleone G, Giaccari A, Fernandez Real JM, Federici M (2014) IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity. Diabetes 63:2086-2096
41. Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68:437-446
42. Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S, Mathis D (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930-939
43. Fink LN, Costford SR, Lee YS, Jensen TE, Bilan PJ, Oberbach A, Bluher M, Olefsky JM, Sams A, Klip A (2014) Pro-inflammatory macrophages increase in skeletal muscle of high fat-Fed mice and correlate with metabolic risk markers in humans. Obesity (Silver Spring) 22:747-757
44. Finucane OM, Reynolds CM, McGillicuddy FC, Harford KA, Morrison M, Baugh J, Roche HM (2014) Macrophage migration inhibitory factor deficiency ameliorates high-fat diet induced insulin resistance in mice with reduced adipose inflammation and hepatic steatosis. PLoS One 9:e113369
45. Fromme T, Klingenspor M (2011) Uncoupling protein 1 expression and high-fat diets. Am J Physiol Regul Integr Comp Physiol 300:R1-R8
46. Fuster JJ, Zuriaga MA, Thi-Minh Ngo D, Farb MG, Aprahamian T, Yamaguchi TP, Gokce N, Walsh K (2014) Non-canonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion. Diabetes 64: 1235-1248
47. Gadd VL, Skoien R, Powell EE, Fagan KJ, Winterford C, Horsfall L, Irvine K, Clouston AD (2014) The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology 59:1393-1405
48. Getz GS, Vanderlaan PA, Reardon CA (2011) Natural killer T cells in lipoprotein metabolism and atherosclerosis. Thromb Haemost 106:814-819
49. Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23-35
50. Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593-604
51. Gri G, Frossi B, D’Inca F, Danelli L, Betto E, Mion F, Sibilano R, Pucillo C (2012) Mast cell: an emerging partner in immune interaction. Front Immunol 3:120
52. Hamada M, Abe M, Miyake T, Kawasaki K, Tada F, Furukawa S, Matsuura B, Hiasa Y, Onji M (2011) B cell-activating factor controls the production of adipokines and induces insulin resistance. Obesity (Silver Spring) 19:1915-1922
53. Harley IT, Stankiewicz TE, Giles DA, Softic S, Flick LM, Cappelletti M, Sheridan R, Xanthakos SA, Steinbrecher KA, Sartor RB, Kohli R, Karp CL, Divanovic S (2014) IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology 59:1830-1839
54. Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252-1263
55. 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 (2013) Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice. Hepatology 58:589-602
56. Hirai S, Ohyane C, Kim YI, Lin S, Goto T, Takahashi N, Kim CS, Kang J, Yu R, Kawada T (2014) Involvement of mast cells in adipose tissue fibrosis. Am J Physiol Endocrinol Metab 306: E247-E255
57. Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333-336
58. Hivroz C, Chemin K, Tourret M, Bohineust A (2012) Crosstalk between T lymphocytes and dendritic cells. Crit Rev Immunol 32:139-155
59. Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, Scott DK, O’Doherty RM (2010) Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes 59:347-357
60. Ibusuki R, Uto H, Arima S, Mawatari S, Setoguchi Y, Iwashita Y, Hashimoto S, Maeda T, Tanoue S, Kanmura S, Oketani M, Ido A, Tsubouchi H (2013) Transgenic expression of human neutrophil peptide-1 enhances hepatic fibrosis in mice fed a choline-deficient, L-amino acid-defined diet. Liver Int 33:1549-1556
61. Ichiki T, Sunagawa K (2014) Novel roles of hypoxia response system in glucose metabolism and obesity. Trends Cardiovasc Med 24:197-201
62. Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T, Yengo L, Kimura I, Leloire A, Liu N, Iida K, Choquet H, Besnard P, Lecoeur C, Vivequin S, Ayukawa K, Takeuchi M, Ozawa K, Tauber M, Maffeis C, Morandi A, Buzzetti R, Elliott P, Pouta A, Jarvelin MR, Korner A, Kiess W, Pigeyre M, Caiazzo R, Van Hul W, Van Gaal L, Horber F, Balkau B, Levy-Marchal C, Rouskas K, Kouvatsi A, Hebebrand J, Hinney A, Scherag A, Pattou F, Meyre D, Koshimizu TA, Wolowczuk I, Tsujimoto G, Froguel P (2012) Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483:350-354
63. Ilan Y, Maron R, Tukpah AM, Maioli TU, Murugaiyan G, Yang K, Wu HY, Weiner HL (2010) Induction of regulatory T cells decreases adipose inflammation and alleviates insulin resistance in ob/ob mice. Proc Natl Acad Sci U S A 107:9765-9770
64. Inouye KE, Shi H, Howard JK, Daly CH, Lord GM, Rollins BJ, Flier JS (2007) Absence of CC chemokine ligand 2 does not limit obesity-associated infiltration of macrophages into adipose tissue. Diabetes 56:2242-2250
65. Inzaugarat ME, Ferreyra Solari NE, Billordo LA, Abecasis R, Gadano AC, Chernavsky AC (2011) Altered phenotype and functionality of circulating immune cells characterize adult patients with nonalcoholic steatohepatitis. J Clin Immunol 31:1120-1130
66. Ioan-Facsinay A, Kwekkeboom JC, Westhoff S, Giera M, Rombouts Y, van Harmelen V, Huizinga TW, Deelder A, Kloppenburg M, Toes RE (2013) Adipocyte-derived lipids modulate CD4+ T-cell function. Eur J Immunol 43:1578-1587
67. Ishijima Y, Ohmori S, Ohneda K (2014) Mast cell deficiency results in the accumulation of preadipocytes in adipose tissue in both obese and non-obese mice. FEBS Open Bio 4:18-24
68. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121-1133
69. Iyer A, Lim J, Poudyal H, Reid RC, Suen JY, Webster J, Prins JB, Whitehead JP, Fairlie DP, Brown L (2012) An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats. Diabetes 61:2320-2329
70. Jaensson E, Uronen-Hansson H, Pabst O, Eksteen B, Tian J, Coombes JL, Berg PL, Davidsson T, Powrie F, Johansson-Lindbom B, Agace WW (2008) Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 205:2139-2149
71. Jiang E, Perrard XD, Yang D, Khan IM, Perrard JL, Smith CW, Ballantyne CM, Wu H (2014) Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue. Arterioscler Thromb Vasc Biol 34:34-43
72. Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840-846
73. Kaminski DA, Randall TD (2010) Adaptive immunity and adipose tissue biology. Trends Immunol 31:384-390
74. Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116:1494-1505
75. Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH (2008) Adipocytederived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 7:485-495
76. Kawasaki K, Abe M, Tada F, Tokumoto Y, Chen S, Miyake T, Furukawa S, Matsuura B, Hiasa Y, Onji M (2013) Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity. Lab Invest 93:311-321
77. Kelly A, Fahey R, Fletcher JM, Keogh C, Carroll AG, Siddachari R, Geoghegan J, Hegarty JE, Ryan EJ, O’Farrelly C (2014) CD141(+) myeloid dendritic cells are enriched in healthy human liver. J Hepatol 60:135-142
78. Khan IM, Dai Perrard XY, Perrard JL, Mansoori A, Smith CW, Wu H, Ballantyne CM (2014a) Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4 + and CD8+ T cell deficiency. Atherosclerosis 233:419-428
79. Khan MT, Nieuwdorp M, Backhed F (2014b) Microbial modulation of insulin sensitivity. Cell Metab 20:753-760
80. Kim DH, Do MS (2015) BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity. Exp Mol Med 47:e129
81. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, Fischer-Posovszky P, Barth TF, Dragun D, Skurk T, Hauner H, Bluher M, Unger T, Wolf AM, Knippschild U, Hombach V, Marx N (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304-1310
82. Kita H (2011) Eosinophils: multifaceted biological properties and roles in health and disease. Immunol Rev 242:161-177
83. Koenen TB, Stienstra R, van Tits LJ, Joosten LA, van Velzen JF, Hijmans A, Pol JA, van der Vliet JA, Netea MG, Tack CJ, Stalenhoef AF, de Graaf J (2011) The inflammasome and caspase-1 activation: a new mechanism underlying increased inflammatory activity in human visceral adipose tissue. Endocrinology 152:3769-3778
84. Kondo T, Toyoshima Y, Ishii Y, Kyuwa S (2013) Natural killer T cells in adipose tissue are activated in lean mice. Exp Anim 62:319-328
85. Kordonowy LL, Burg E, Lenox CC, Gauthier LM, Petty JM, Antkowiak M, Palvinskaya T, Ubags N, Rincon M, Dixon AE, Vernooy JH, Fessler MB, Poynter ME, Suratt BT (2012)Obesity is associated with neutrophil dysfunction and attenuation of murine acute lung injury. Am J Respir Cell Mol Biol 47:120-127
86. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells. Annu Rev Immunol 27:485-517
87. Kraakman MJ, Murphy AJ, Jandeleit-Dahm K, Kammoun HL (2014) Macrophage polarization in obesity and type 2 diabetes: weighing down our understanding of macrophage function? Front Immunol 5:470
88. Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance. Front Endocrinol (Lausanne) 4:71
89. Lanthier N, Molendi-Coste O, Horsmans Y, van Rooijen N, Cani PD, Leclercq IA (2010) Kupffer cell activation is a causal factor for hepatic insulin resistance. Am J Physiol Gastrointest Liver Physiol 298:G107-G116
90. Lee BC, Lee J (2014) Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta 1842:446-462
91. Lee MW, Odegaard JI, Mukundan L, Qiu Y, Molofsky AB, Nussbaum JC, Yun K, Locksley RM, Chawla A (2015) Activated type 2 innate lymphoid cells regulate beige fat biogenesis. Cell 160:74-87
92. Leroux A, Ferrere G, Godie V, Cailleux F, Renoud ML, Gaudin F, Naveau S, Prevot S, Makhzami S, Perlemuter G, Cassard-Doulcier AM (2012) Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis. J Hepatol 57:141-149
93. Li L, Huang L, Vergis AL, Ye H, Bajwa A, Narayan V, Strieter RM, Rosin DL, Okusa MD (2010) IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration in mouse kidney ischemia-reperfusion injury. J Clin Invest 120:331-342
94. Liang W, Lindeman JH, Menke AL, Koonen DP, Morrison M, Havekes LM, van den Hoek AM, Kleemann R (2014) Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1beta-induced chronic inflammation. Lab Invest 94:491-502
95. Liao X, Sharma N, Kapadia F, Zhou G, Lu Y, Hong H, Paruchuri K, Mahabeleshwar GH, Dalmas E, Venteclef N, Flask CA, Kim J, Doreian BW, Lu KQ, Kaestner KH, Hamik A, Clement K, Jain MK (2011) Kruppel-like factor 4 regulates macrophage polarization. J Clin Invest 121:2736-2749
96. Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P, Virtanen KA, Beuschlein F, Persson A, Borga M, Enerback S (2013) Evidence for two types of brown adipose tissue in humans. Nat Med 19:631-634
97. Lim J, Iyer A, Liu L, Suen JY, Lohman RJ, Seow V, Yau MK, Brown L, Fairlie DP (2013) Dietinduced obesity, adipose inflammation, and metabolic dysfunction correlating with PAR2 expression are attenuated by PAR2 antagonism. FASEB J 27:4757-4767
98. Liu J, Divoux A, Sun J, Zhang J, Clement K, Glickman JN, Sukhova GK, Wolters PJ, Du J, Gorgun CZ, Doria A, Libby P, Blumberg RS, Kahn BB, Hotamisligil GS, Shi GP (2009) Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat Med 15:940-945
99. Locatelli I, Sutti S, Vacchiano M, Bozzola C, Albano E (2013) NF-kappaB1 deficiency stimulates the progression of non-alcoholic steatohepatitis (NASH) in mice by promoting NKT-cellmediated responses. Clin Sci (Lond) 124:279-287
100. Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117:175-184
101. Lumeng CN, DelProposto JB, Westcott DJ, Saltiel AR (2008) Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes 57:3239-3246
102. Lumeng CN, Maillard I, Saltiel AR (2009) T-ing up inflammation in fat. Nat Med 15:846-847
103. Ma X, Hua J, Mohamood AR, Hamad AR, Ravi R, Li Z (2007) A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury. Hepatology 46:1519-1529
104. Mallevaey T, Clarke AJ, Scott-Browne JP, Young MH, Roisman LC, Pellicci DG, Patel O, Vivian JP, Matsuda JL, McCluskey J, Godfrey DI, Marrack P, Rossjohn J, Gapin L (2011) A molecular basis for NKT cell recognition of CD1d-self-antigen. Immunity 34:315-326
105. Mantell BS, Stefanovic-Racic M, Yang X, Dedousis N, Sipula IJ, O’Doherty RM (2011) Mice lacking NKT cells but with a complete complement of CD8+ T-cells are not protected against the metabolic abnormalities of diet-induced obesity. PLoS One 6:e19831
106. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, LocatiM(2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25:677-686
107. Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519-531
108. Martinez FO, Helming L, Gordon S (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27:451-483
109. Martin-Murphy BV, You Q, Wang H, De La Houssaye BA, Reilly TP, Friedman JE, Ju C (2014) Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding. PLoS One 9:e80949
110. Matarese G, Di Giacomo A, Sanna V, Lord GM, Howard JK, Di Tuoro A, Bloom SR, Lechler RI, Zappacosta S, Fontana S (2001) Requirement for leptin in the induction and progression of autoimmune encephalomyelitis. J Immunol 166:5909-5916
111. Mazza C, Malissen B (2007) What guides MHC-restricted TCR recognition? Semin Immunol 19:225-235
112. McLaughlin T, Liu LF, Lamendola C, Shen L, Morton J, Rivas H, Winer D, Tolentino L, Choi O, Zhang H, Hui Yen Chng M, Engleman E (2014) T-cell profile in adipose tissue is associated with insulin resistance and systemic inflammation in humans. Arterioscler Thromb Vasc Biol 34:2637-2643
113. 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 (2012) Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology 143:765-76.e1-3
114. Merad M, Manz MG (2009) Dendritic cell homeostasis. Blood 113:3418-3427
115. Miura K, Yang L, van Rooijen N, Ohnishi H, Seki E (2012) Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR 2. Am J Physiol Gastrointest Liver Physiol 302:G1310-G1321
116. Miyake T, Akbar SM, Yoshida O, Chen S, Hiasa Y, Matsuura B, Abe M, Onji M (2010) Impaired dendritic cell functions disrupt antigen-specific adaptive immune responses in mice with nonalcoholic fatty liver disease. J Gastroenterol 45:859-867
117. Molofsky AB, Nussbaum JC, Liang HE, Van Dyken SJ, Cheng LE, Mohapatra A, Chawla A, Locksley RM (2013) Innate lymphoid type 2 cells sustain visceral adipose tissue eosinophils and alternatively activated macrophages. J Exp Med 210:535-549
118. Monk JM, Hou TY, Turk HF, Weeks B, Wu C, McMurray DN, Chapkin RS (2013) Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis. PLoS One 7:e49739
119. Morris DL, Cho KW, Delproposto JL, Oatmen KE, Geletka LM, Martinez-Santibanez G, Singer K, Lumeng CN (2013) Adipose tissue macrophages function as antigen-presenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes 62:2762-2772
120. Murahovschi V, Pivovarova O, Ilkavets I, Dmitrieva RM, Docke S, Keyhani-Nejad F, Gogebakan O, Osterhoff M, Kemper M, Hornemann S, Markova M, Kloting N, Stockmann M, Weickert MO, Lamounier-Zepter V, Neuhaus P, Konradi A, Dooley S, von Loeffelholz C, Bluher M, Pfeiffer AF, Rudovich N (2014) WISP1 is a novel adipokine linked to inflammation in obesity. Diabetes 64:856-866
121. Musilli C, Paccosi S, Pala L, Gerlini G, Ledda F, Mugelli A, Rotella CM, Parenti A (2011) Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients. Mol Immunol 49:234-238
122. Myers MG Jr, Leibel RL, Seeley RJ, Schwartz MW (2010) Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 21:643-651
123. Nguyen KD, Qiu Y, Cui X, Goh YP, Mwangi J, David T, Mukundan L, Brombacher F, Locksley RM, Chawla A (2011) Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis. Nature 480:104-108
124. Nijhuis J, Rensen SS, Slaats Y, van Dielen FM, Buurman WA, Greve JW (2009) Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity (Silver Spring) 17:2014-2018
125. Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914-920
126. O’Rourke RW, Metcalf MD, White AE, Madala A, Winters BR, Maizlin II, Jobe BA, Roberts CT Jr, Slifka MK, Marks DL (2009) Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue. Int J Obes (Lond) 33:978-990
127. O’Shea D, Corrigan M, Dunne MR, Jackson R, Woods C, Gaoatswe G, Moynagh PN, O’Connell J, Hogan AE (2013) Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection. Int J Obes (Lond) 37:1510-1513
128. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, Mukundan L, Red Eagle A, Vats D, Brombacher F, Ferrante AW, Chawla A (2007) Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 447:1116-1120
129. Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S, Andoh Y, Fujii S, Iwabuchi K, Onoe K, Tsutsui H (2010) Natural killer T cells are involved in adipose tissues inflammation and glucose intolerance in diet-induced obese mice. Arterioscler Thromb Vasc Biol 30:193-199
130. Orr JS, Puglisi MJ, Ellacott KL, Lumeng CN, Wasserman DH, Hasty AH (2012) Toll-like receptor 4 deficiency promotes the alternative activation of adipose tissue macrophages. Diabetes 61:2718-2727
131. Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18:363-374
132. Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85-97
133. Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S (2012) Fetuin-A acts as an endogenous ligand of TLR4 to promote lipidinduced insulin resistance. Nat Med 18:1279-1285
134. Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG (2008) Ablation of CD11cpositive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 8:301-309
135. Phieler J, Chung KJ, Chatzigeorgiou A, Klotzsche-von Ameln A, Garcia-Martin R, Sprott D, Moisidou M, Tzanavari T, Ludwig B, Baraban E, Ehrhart-Bornstein M, Bornstein SR, Mziaut H, Solimena M, Karalis KP, Economopoulou M, Lambris JD, Chavakis T (2013) The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance. J Immunol 191:4367-4374
136. Piccirillo CA, d’Hennezel E, Sgouroudis E, Yurchenko E (2008) CD4+Foxp3+ regulatory T cells in the control of autoimmunity: in vivo veritas. Curr Opin Immunol 20:655-662
137. Pulendran B, Artis D (2012) New paradigms in type 2 immunity. Science 337:431-435
138. Qiu Y, Nguyen KD, Odegaard JI, Cui X, Tian X, Locksley RM, Palmiter RD, Chawla A (2014) Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell 157:1292-1308
139. Ramkhelawon B, Hennessy EJ, Menager M, Ray TD, Sheedy FJ, Hutchison S, Wanschel A, Oldebeken S, Geoffrion M, Spiro W, Miller G, McPherson R, Rayner KJ, Moore KJ (2014)Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med 20:377-384
140. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I, Jedrychowski MP, Ruas JL, Wrann CD, Lo JC, Camera DM, Lachey J, Gygi S, Seehra J, Hawley JA, Spiegelman BM (2014) Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 157:1279-1291
141. Raphael I, Nalawade S, Eagar TN, Forsthuber TG (2014) T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine doi: 10.1016/j.cyto.2014.09. 011 (Epub ahead of print)
142. Rausch ME, Weisberg S, Vardhana P, Tortoriello DV (2008) Obesity in C57BL/6J mice is characterized by adipose tissue hypoxia and cytotoxic T-cell infiltration. Int J Obes (Lond) 32:451-463
143. Rensen SS, Slaats Y, Nijhuis J, Jans A, Bieghs V, Driessen A, Malle E, Greve JW, Buurman WA (2009) Increased hepatic myeloperoxidase activity in obese subjects with nonalcoholic steatohepatitis. Am J Pathol 175:1473-1482
144. Rensen SS, Bieghs V, Xanthoulea S, Arfianti E, Bakker JA, Shiri-Sverdlov R, Hofker MH, Greve JW, Buurman WA (2012) Neutrophil-derived myeloperoxidase aggravates non-alcoholic steatohepatitis in low-density lipoprotein receptor-deficient mice. PLoS One 7:e52411
145. Ricardo-Gonzalez RR, Red Eagle A, Odegaard JI, Jouihan H, Morel CR, Heredia JE, Mukundan L, Wu D, Locksley RM, Chawla A (2010) IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity. Proc Natl Acad Sci U S A 107:22617-22622
146. Ricciardi-Castagnoli P, Granucci F (2002) Opinion: interpretation of the complexity of innate immune responses by functional genomics. Nat Rev Immunol 2:881-889
147. Rocha VZ, Folco EJ, Sukhova G, Shimizu K, Gotsman I, Vernon AH, Libby P (2008) Interferongamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ Res 103:467-476
148. Rossato M, Granzotto M, Macchi V, Porzionato A, Petrelli L, Calcagno A, Vencato J, De Stefani D, Silvestrin V, Rizzuto R, Bassetto F, De Caro R, Vettor R (2014) Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production. Mol Cell Endocrinol 383:137-146
149. Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58:1526-1531
150. Schenk S, Saberi M, Olefsky JM (2008) Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 118:2992-3002
151. Seijkens T, Kusters P, Chatzigeorgiou A, Chavakis T, Lutgens E (2014) Immune cell crosstalk in obesity: a key role for costimulation? Diabetes 63:3982-3991
152. Seth RK, Das S, Kumar A, Chanda A, Kadiiska MB, Michelotti G, Manautou J, Diehl AM, Chatterjee S (2014) CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8 + T cells aid progression of environment-linked nonalcoholic steatohepatitis. Toxicol Appl Pharmacol 274:42-54
153. Shan J, Feng L, Sun G, Chen P, Zhou Y, Xia M, Li H, Li Y (2014) Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells. Immunobiology 220:510-517
154. Shen L, Chng MH, Alonso MN, Yuan R, Winer DA, Engleman EG (2014) B-1a lymphocytes attenuate insulin resistance. Diabetes 64:593-603
155. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:3015-3025
156. Shin JH, Shin DW, Noh M (2009) Interleukin-17A inhibits adipocyte differentiation in human mesenchymal stem cells and regulates pro-inflammatory responses in adipocytes. Biochem Pharmacol 77:1835-1844
157. Sim AT, Ludowyke RI, Verrills NM (2006) Mast cell function: regulation of degranulation by serine/threonine phosphatases. Pharmacol Ther 112:425-439
158. Soderberg C, Marmur J, Eckes K, Glaumann H, Sallberg M, Frelin L, Rosenberg P, Stal P, Hultcrantz R (2011) Microvesicular fat, inter cellular adhesion molecule-1 and regulatory T-lymphocytes are of importance for the inflammatory process in livers with non-alcoholic steatohepatitis. APMIS 119:412-420
159. Spencer LA, Weller PF (2010) Eosinophils and Th2 immunity: contemporary insights. Immunol Cell Biol 88:250-256
160. Stefanovic-Racic M, Yang X, Turner MS, Mantell BS, Stolz DB, Sumpter TL, Sipula IJ, Dedousis N, Scott DK, Morel PA, Thomson AW, O’Doherty RM (2012) Dendritic cells promote macrophage infiltration and comprise a substantial proportion of obesity-associated increases in CD11c+ cells in adipose tissue and liver. Diabetes 61:2330-2339
161. Stein M, Keshav S, Harris N, Gordon S (1992) Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 176:287-292
162. Stienstra R, Saudale F, Duval C, Keshtkar S, Groener JE, van Rooijen N, Staels B, Kersten S, Muller M (2010) Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity. Hepatology 51:511-522
163. Stockinger B, Veldhoen M (2007) Differentiation and function of Th17 T cells. Curr Opin Immunol 19:281-286
164. Stolarczyk E, Vong CT, Perucha E, Jackson I, Cawthorne MA, Wargent ET, Powell N, Canavan JB, Lord GM, Howard JK (2013) Improved insulin sensitivity despite increased visceral adiposity in mice deficient for the immune cell transcription factor T-bet. Cell Metab 17:520-533
165. Subramanian S, Chait A (2012) Hypertriglyceridemia secondary to obesity and diabetes. Biochim Biophys Acta 1821:819-825
166. Surmi BK, Hasty AH (2008) Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Futur Lipidol 3:545-556
167. Sutti S, Jindal A, Locatelli I, Vacchiano M, Gigliotti L, Bozzola C, Albano E (2014) Adaptive immune responses triggered by oxidative stress contribute to hepatic inflammation in NASH. Hepatology 59:886-897
168. Sutton CE, Mielke LA, Mills KH (2012) IL-17-producing gammadelta T cells and innate lymphoid cells. Eur J Immunol 42:2221-2231
169. 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 (2010) Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 51:1998-2007
170. 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 (2012) NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease. Gut 61:1323-1329
171. Tajiri K, Shimizu Y, Tsuneyama K, Sugiyama T (2009) Role of liver-infiltrating CD3+CD56+ natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 21:673-680
172. Taleb S, Herbin O, Ait-Oufella H, Verreth W, Gourdy P, Barateau V, Merval R, Esposito B, Clement K, Holvoet P, Tedgui A, Mallat Z (2007) Defective leptin/leptin receptor signaling improves regulatory T cell immune response and protects mice from atherosclerosis. Arterioscler Thromb Vasc Biol 27:2691-2698
173. Talukdar S, da Oh Y, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, Ofrecio J, Lin M, Brenner MB, Olefsky JM (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407-1412
174. Tanaka A, Nomura Y, Matsuda A, Ohmori K, Matsuda H (2011) Mast cells function as an alternative modulator of adipogenesis through 15-deoxy-delta-12, 14-prostaglandin J 2. Am J Physiol Cell Physiol 301:C1360-C1367
175. 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 (2011) Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease. Clin Exp Immunol 166:281-290
176. Tashiro K, Takai S, Jin D, Yamamoto H, Komeda K, Hayashi M, Tanaka K, Tanigawa N, Miyazaki M (2010) Chymase inhibitor prevents the nonalcoholic steatohepatitis in hamsters fed a methionine-and choline-deficient diet. Hepatol Res 40:514-523
177. Tosello-Trampont AC, Landes SG, Nguyen V, Novobrantseva TI, Hahn YS (2012) Kupffer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-alpha production. J Biol Chem 287:40161-40172
178. Triggiani M, Granata F, Frattini A, Marone G (2006) Activation of human inflammatory cells by secreted phospholipases A 2. Biochim Biophys Acta 1761:1289-1300
179. Tsuruda T, Kato J, Hatakeyama K, Kojima K, Yano M, Yano Y, Nakamura K, Nakamura-Uchiyama F, Matsushima Y, Imamura T, Onitsuka T, Asada Y, Nawa Y, Eto T, Kitamura K (2008) Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm. Circ Res 102:1368-1377
180. van den Berg SM, Seijkens TT, Kusters PJ, Zarzycka B, Beckers L, den Toom M, Gijbels MJ, Chatzigeorgiou A, Weber C, de Winther MP, Chavakis T, Nicolaes GA, Lutgens E (2014) Blocking CD40-TRAF6 interactions by small-molecule inhibitor 6860766 ameliorates the complications of diet-induced obesity in mice. Int J Obes (Lond) doi: 10.1038/ijo.2014.198 (Epub ahead of print)
181. Van Dyken SJ, Locksley RM (2013) Interleukin-4-and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol 31:317-343
182. Vasanthakumar A, Moro K, Xin A, Liao Y, Gloury R, Kawamoto S, Fagarasan S, Mielke LA, Afshar-Sterle S, Masters SL, Nakae S, Saito H, Wentworth JM, Li P, Liao W, Leonard WJ, Smyth GK, Shi W, Nutt SL, Koyasu S, Kallies A (2015) The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells. Nat Immunol 16:276-285
183. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360:1518-1525
184. Wagner NM, Brandhorst G, Czepluch F, Lankeit M, Eberle C, Herzberg S, Faustin V, Riggert J, Oellerich M, Hasenfuss G, Konstantinides S, Schafer K (2013) Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk. Obesity (Silver Spring) 21:461-468
185. Wan YY, Flavell RA (2009) How diverse-CD4 effector T cells and their functions. J Mol Cell Biol 1:20-36
186. Wang Q, Xie Z, Zhang W, Zhou J, Wu Y, Zhang M, Zhu H, Zou MH (2014) Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance. Diabetes 63:4172-4185
187. Wehr A, Baeck C, Heymann F, Niemietz PM, Hammerich L, Martin C, Zimmermann HW, Pack O, Gassler N, Hittatiya K, Ludwig A, Luedde T, Trautwein C, Tacke F (2013) Chemokine receptor CXCR6-dependent hepatic NK T cell accumulation promotes inflammation and liver fibrosis. J Immunol 190:5226-5236
188. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796-1808
189. Weitman ES, Aschen SZ, Farias-Eisner G, Albano N, Cuzzone DA, Ghanta S, Zampell JC, Thorek D, Mehrara BJ (2013) Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes. PLoS One 8:e70703
190. Westcott DJ, Delproposto JB, Geletka LM, Wang T, Singer K, Saltiel AR, Lumeng CN (2009) MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. J Exp Med 206:3143-3156
191. 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 (2009a) Normalization of obesity-associated insulin resistance through immunotherapy. Nat Med 15:921-929
192. Winer S, Paltser G, Chan Y, Tsui H, Engleman E, Winer D, Dosch HM (2009b) Obesity predisposes to Th17 bias. Eur J Immunol 39:2629-2635
193. 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 (2011) B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat Med 17:610-617
194. Winer DA, Winer S, Chng MH, Shen L, Engleman EG (2014) B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance. Cell Mol Life Sci 71:1033-1043
195. Wing JB, Sakaguchi S (2012) Multiple treg suppressive modules and their adaptability. Front Immunol 3:178
196. Wolf MJ, Adili A, Piotrowitz K, Abdullah Z, Boege Y, Stemmer K, Ringelhan M, Simonavicius N, Egger M, Wohlleber D, Lorentzen A, Einer C, Schulz S, Clavel T, Protzer U, Thiele C, Zischka H, Moch H, Tschop M, Tumanov AV, Haller D, Unger K, Karin M, Kopf M, Knolle P, Weber A, Heikenwalder M (2014) Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes. Cancer Cell 26:549-564
197. Wong VW, Wong GL, Choi PC, Chan AW, Li MK, Chan HY, Chim AM, Yu J, Sung JJ, Chan HL (2010) Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 59:969-974
198. Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE (2013) From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 10:627-636
199. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM (2011) Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332:243-247
200. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM (2012a) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366-376
201. Wu L, Parekh VV, Gabriel CL, Bracy DP, Marks-Shulman PA, Tamboli RA, Kim S, Mendez-Fernandez YV, Besra GS, Lomenick JP, Williams B, Wasserman DH, Van Kaer L (2012b) Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice. Proc Natl Acad Sci U S A 109:E1143-E1152
202. Xu JM, Shi GP (2012) Emerging role of mast cells and macrophages in cardiovascular and metabolic diseases. Endocr Rev 33:71-108
203. Yamagata H, Ikejima K, Takeda K, Aoyama T, Kon K, Okumura K, Watanabe S (2013) Altered expression and function of hepatic natural killer T cells in obese and diabetic KK-A(y) mice. Hepatol Res 43:276-288
204. Yekollu SK, Thomas R, O’Sullivan B (2011) Targeting curcusomes to inflammatory dendritic cells inhibits NF-kappaB and improves insulin resistance in obese mice. Diabetes 60:2928-2938
205. Yilmaz H, Ucan B, Sayki M, Unsal I, Sahin M, Ozbek M, Delibasi T (2014) Usefulness of the neutrophil-to-lymphocyte ratio to prediction of type 2 diabetes mellitus in morbid obesity. Diabetes Metab Syndr doi: 10.1016/j.dsx.2014.04.009 (Epub ahead of print)
206. Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H (2012) SOCS, inflammation, and autoimmunity. Front Immunol 3:20
207. Yu Y, Liu Y, Shi FD, Zou H, Matarese G, La Cava A (2013) Cutting edge: leptin-induced RORgammat expression in CD4+ T cells promotes Th17 responses in systemic lupus erythematosus. J Immunol 190:3054-3058
208. Zeyda M, Huber J, Prager G, Stulnig TM (2011) Inflammation correlates with markers of T-cell subsets including regulatory T cells in adipose tissue from obese patients. Obesity (Silver Spring) 19:743-748
209. Zhao L, de Qiu K, Ma X (2010) Th17 cells: the emerging reciprocal partner of regulatory T cells in the liver. J Dig Dis 11:126-133
210. Zhong J, Rao X, Braunstein Z, Taylor A, Narula V, Hazey J, Mikami D, Needleman B, Rutsky J, Sun Q, Deiuliis JA, Satoskar AR, Rajagopalan S (2014) T-cell costimulation protects obesityinduced adipose inflammation and insulin resistance. Diabetes 63:1289-1302
211. Zhu J, Yamane H, Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol 28:445-489
212. Zhu L, Wu Y, Wei H, Xing X, Zhan N, Xiong H, Peng B (2011) IL-17R activation of human periodontal ligament fibroblasts induces IL-23 p19 production: differential involvement of NF-kappaB versus JNK/AP-1 pathways. Mol Immunol 48:647-656
213. Zuniga LA, Shen WJ, Joyce-Shaikh B, Pyatnova EA, Richards AG, Thom C, Andrade SM, Cua DJ, Kraemer FB, Butcher EC (2010) IL-17 regulates adipogenesis, glucose homeostasis, and obesity. J Immunol 185:6947-6959