Skip to main content
SpringerLink
Log in

Transcriptional control of macrophage polarisation in type 2 diabetes

  • Review
  • Published:
Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

Type-2 diabetes (T2D) is considered today as an inflammatory disease. Inflammatory processes in T2D are orchestrated by macrophage activation in different organs. Macrophages undergo classical M1 pro-inflammatory or alternative M2 anti-inflammatory activation in response to tissue microenvironmental signals. These subsets of macrophages are characterised by their expression of cell surface markers, secreted cytokines and chemokines. Transcriptional regulation is central to the polarisation of macrophages, and several major pathways have been described as essential to promote the expression of specific genes, which dictate the functional polarisation of macrophages. In this review, we summarise the current knowledge of transcriptional control of macrophage polarisation and the role this plays in development of insulin resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Rubartelli A, Lotze MT, Latz E, Manfredi A (2013) Mechanisms of sterile inflammation. Front Immunol 4:398

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gordon S, Martinez-Pomares L (2017) Physiological roles of macrophages. Pflugers Arch 469:365–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Boutens L, Stienstra R (2016) Adipose tissue macrophages: going off track during obesity. Diabetologia 59:879–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tesch GH (2007) Role of macrophages in complications of type 2 diabetes. Clin Exp Pharmacol Physiol 34:1016–1019

    Article  CAS  PubMed  Google Scholar 

  5. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT, Sahebkar A (2018) Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 233:6425–6440

    Article  CAS  PubMed  Google Scholar 

  6. Gieseck RL 3rd, Wilson MS, Wynn TA (2018) Type 2 immunity in tissue repair and fibrosis. Nat Rev Immunol 18:62–76

    Article  CAS  PubMed  Google Scholar 

  7. Kratz M, Coats BR, Hisert KB, Hagman D, Mutskov V, Peris E, Schoenfelt KQ, Kuzma JN, Larson I, Billing PS, Landerholm RW, Crouthamel M, Gozal D, Hwang S, Singh PK, Becker L (2014) Metabolic dysfunction drives a mechanistically distinct proinflammatory phenotype in adipose tissue macrophages. Cell Metab 20:614–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Coats BR, Schoenfelt KQ, Barbosa-Lorenzi VC, Peris E, Cui C, Hoffman A, Zhou G, Fernandez S, Zhai L, Hall BA, Haka AS, Shah AM, Reardon CA, Brady MJ, Rhodes CJ, Maxfield FR, Becker L (2017) Metabolically activated adipose tissue macrophages perform detrimental and beneficial functions during diet-induced obesity. Cell Rep 20:3149–3161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Aravindhan V, Madhumitha H (2016) Metainflammation in diabetic coronary artery disease: emerging role of innate and adaptive immune responses. J Diabetes Res 2016:6264149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yamamoto Y, Yamamoto H (2013) RAGE-mediated inflammation, type 2 diabetes, and diabetic vascular complication. Front Endocrinol (Lausanne) 4:105

    Article  Google Scholar 

  11. Hoeksema MA, de Winther MP (2016) Epigenetic regulation of monocyte and macrophage function. Antioxid Redox Signal 25:758–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brennan JJ, Gilmore TD (2018) Evolutionary origins of toll-like receptor signaling. Mol Biol Evol 35:1576–1587

    Article  CAS  PubMed  Google Scholar 

  13. Ermis Karaali Z, Candan G, Aktuglu MB, Velet M, Ergen A (2019) Toll-like receptor 2 (TLR-2) gene polymorphisms in type 2 diabetes mellitus. Cell J 20:559–563

    PubMed  Google Scholar 

  14. Gupta S, Maratha A, Siednienko J, Natarajan A, Gajanayake T, Hoashi S, Miggin S (2017) Analysis of inflammatory cytokine and TLR expression levels in type 2 diabetes with complications. Sci Rep 7:7633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Haversen L, Danielsson KN, Fogelstrand L, Wiklund O (2009) Induction of proinflammatory cytokines by long-chain saturated fatty acids in human macrophages. Atherosclerosis 202:382–393

    Article  CAS  PubMed  Google Scholar 

  16. Filgueiras LR, Brandt SL, Ramalho TR, Jancar S, Serezani CH (2017) Imbalance between HDAC and HAT activities drives aberrant STAT1/MyD88 expression in macrophages from type 1 diabetic mice. J Diabetes Complicat 31:334–339

    Article  Google Scholar 

  17. Reardon CA, Lingaraju A, Schoenfelt KQ, Zhou G, Cui C, Jacobs-El H, Babenko I, Hoofnagle A, Czyz D, Shuman H, Vaisar T, Becker L (2018) Obesity and insulin resistance promote atherosclerosis through an IFNgamma-regulated macrophage protein network. Cell Rep 23:3021–3030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Vasamsetti SB, Karnewar S, Kanugula AK, Thatipalli AR, Kumar JM, Kotamraju S (2015) Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes 64:2028–2041

    Article  CAS  PubMed  Google Scholar 

  19. Tang C, Houston BA, Storey C, LeBoeuf RC (2016) Both STAT3 activation and cholesterol efflux contribute to the anti-inflammatory effect of apoA-I/ABCA1 interaction in macrophages. J Lipid Res 57:848–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Desai HR, Sivasubramaniyam T, Revelo XS, Schroer SA, Luk CT, Rikkala PR, Metherel AH, Dodington DW, Park YJ, Kim MJ, Rapps JA, Besla R, Robbins CS, Wagner KU, Bazinet RP, Winer DA, Woo M (2017) Macrophage JAK2 deficiency protects against high-fat diet-induced inflammation. Sci Rep 7:7653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee WJ, Tateya S, Cheng AM, Rizzo-DeLeon N, Wang NF, Handa P, Wilson CL, Clowes AW, Sweet IR, Bomsztyk K, Schwartz MW, Kim F (2015) M2 macrophage polarization mediates anti-inflammatory effects of endothelial nitric oxide signaling. Diabetes 64:2836–2846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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

    Article  PubMed  PubMed Central  Google Scholar 

  23. Solinas G, Becattini B (2017) JNK at the crossroad of obesity, insulin resistance, and cell stress response. Mol Metab 6:174–184

    Article  CAS  PubMed  Google Scholar 

  24. Baker RG, Hayden MS, Ghosh S (2011) NF-kappaB, inflammation, and metabolic disease. Cell Metab 13:11–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Halazonetis TD, Georgopoulos K, Greenberg ME, Leder P (1988) c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell 55:917–924

    Article  CAS  PubMed  Google Scholar 

  26. Ameyar M, Wisniewska M, Weitzman JB (2003) A role for AP-1 in apoptosis: the case for and against. Biochimie 85:747–752

    Article  CAS  PubMed  Google Scholar 

  27. Vesely PW, Staber PB, Hoefler G, Kenner L (2009) Translational regulation mechanisms of AP-1 proteins. Mutat Res 682:7–12

    Article  CAS  PubMed  Google Scholar 

  28. Takahashi M, Yagyu H, Tazoe F, Nagashima S, Ohshiro T, Okada K, Osuga J, Goldberg IJ, Ishibashi S (2013) Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity. J Lipid Res 54:1124–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. Tuncman G, Hirosumi J, Solinas G, Chang L, Karin M, Hotamisligil GS (2006) Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci U S A 103:10741–10746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Solinas G, Vilcu C, Neels JG, Bandyopadhyay GK, Luo JL, Naugler W, Grivennikov S, Wynshaw-Boris A, Scadeng M, Olefsky JM, Karin M (2007) JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 6:386–397

    Article  CAS  PubMed  Google Scholar 

  32. D'Ignazio L, Bandarra D, Rocha S (2016) NF-kappaB and HIF crosstalk in immune responses. FEBS J 283:413–424

    Article  CAS  PubMed  Google Scholar 

  33. Xanthoulea S, Curfs DM, Hofker MH, de Winther MP (2005) Nuclear factor kappa B signaling in macrophage function and atherogenesis. Curr Opin Lipidol 16:536–542

    Article  CAS  PubMed  Google Scholar 

  34. 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

    Article  CAS  PubMed  Google Scholar 

  35. Eguchi J, Wang X, Yu S, Kershaw EE, Chiu PC, Dushay J, Estall JL, Klein U, Maratos-Flier E, Rosen ED (2011) Transcriptional control of adipose lipid handling by IRF4. Cell Metab 13:249–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhao GN, Jiang DS, Li H (2015) Interferon regulatory factors: at the crossroads of immunity, metabolism, and disease. Biochim Biophys Acta 1852:365–378

    Article  CAS  PubMed  Google Scholar 

  37. Chen W, Royer WE Jr (2010) Structural insights into interferon regulatory factor activation. Cell Signal 22:883–887

    Article  CAS  PubMed  Google Scholar 

  38. Gunthner R, Anders HJ (2013) Interferon-regulatory factors determine macrophage phenotype polarization. Mediat Inflamm 2013:731023

    Article  CAS  Google Scholar 

  39. Dalmas E, Toubal A, Alzaid F, Blazek K, Eames HL, Lebozec K, Pini M, Hainault I, Montastier E, Denis RG, Ancel P, Lacombe A, Ling Y, Allatif O, Cruciani-Guglielmacci C, Andre S, Viguerie N, Poitou C, Stich V, Torcivia A, Foufelle F, Luquet S, Aron-Wisnewsky J, Langin D, Clement K, Udalova IA, Venteclef N (2015) Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat Med 21:610–618

    Article  CAS  PubMed  Google Scholar 

  40. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Alzaid F, Lagadec F, Albuquerque M, Ballaire R, Orliaguet L, Hainault I, Blugeon C, Lemoine S, Lehuen A, Saliba DG, Udalova IA, Paradis V, Foufelle F, Venteclef N (2016) IRF5 governs liver macrophage activation that promotes hepatic fibrosis in mice and humans. JCI Insight 1:e88689

    Article  PubMed  PubMed Central  Google Scholar 

  42. Eguchi J, Kong X, Tenta M, Wang X, Kang S, Rosen ED (2013) Interferon regulatory factor 4 regulates obesity-induced inflammation through regulation of adipose tissue macrophage polarization. Diabetes 62:3394–3403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Weiss M, Byrne AJ, Blazek K, Saliba DG, Pease JE, Perocheau D, Feldmann M, Udalova IA (2015) IRF5 controls both acute and chronic inflammation. Proc Natl Acad Sci U S A 112:11001–11006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Saliba DG, Heger A, Eames HL, Oikonomopoulos S, Teixeira A, Blazek K, Androulidaki A, Wong D, Goh FG, Weiss M, Byrne A, Pasparakis M, Ragoussis J, Udalova IA (2014) IRF5:RelA interaction targets inflammatory genes in macrophages. Cell Rep 8:1308–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA (2011) IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol 12:231–238

    Article  CAS  PubMed  Google Scholar 

  46. Zervou MI, Dorschner JM, Ghodke-Puranik Y, Boumpas DT, Niewold TB, Goulielmos GN (2017) Association of IRF5 polymorphisms with increased risk for systemic lupus erythematosus in population of Crete, a southern-eastern European Greek island. Gene 610:9–14

    Article  CAS  PubMed  Google Scholar 

  47. Li P, Lv H, Yang H, Qian JM (2013) IRF5, but not TLR4, DEFB1, or VDR, is associated with the risk of ulcerative colitis in a Han Chinese population. Scand J Gastroenterol 48:1145–1151

    Article  CAS  PubMed  Google Scholar 

  48. Carmona FD, Martin JE, Beretta L, Simeon CP, Carreira PE, Callejas JL, Fernandez-Castro M, Saez-Comet L, Beltran E, Camps MT, Egurbide MV, Spanish Scleroderma G, Airo P, Scorza R, Lunardi C, Hunzelmann N, Riemekasten G, Witte T, Kreuter A, Distler JH, Madhok R, Shiels P, van Laar JM, Fonseca C, Denton C, Herrick A, Worthington J, Schuerwegh AJ, Vonk MC, Voskuyl AE, Radstake TR, Martin J (2013) The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis. PLoS One 8:e54419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shu H, Wong B, Zhou G, Li Y, Berger J, Woods JW, Wright SD, Cai TQ (2000) Activation of PPARalpha or gamma reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commun 267:345–349

    Article  CAS  PubMed  Google Scholar 

  50. Nakamachi T, Nomiyama T, Gizard F, Heywood EB, Jones KL, Zhao Y, Fuentes L, Takebayashi K, Aso Y, Staels B, Inukai T, Bruemmer D (2007) PPARalpha agonists suppress osteopontin expression in macrophages and decrease plasma levels in patients with type 2 diabetes. Diabetes 56:1662–1670

    Article  CAS  PubMed  Google Scholar 

  51. Ye G, Gao H, Wang Z, Lin Y, Liao X, Zhang H, Chi Y, Zhu H, Dong S (2019) PPARalpha and PPARgamma activation attenuates total free fatty acid and triglyceride accumulation in macrophages via the inhibition of Fatp1 expression. Cell Death Dis 10:39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Adhikary T, Wortmann A, Schumann T, Finkernagel F, Lieber S, Roth K, Toth PM, Diederich WE, Nist A, Stiewe T, Kleinesudeik L, Reinartz S, Müller-Brüsselbach S, Müller R. (2015). The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state. Nucleic acids research 43(10):5033–5051. https://doi.org/10.1093/nar/gkv331

  53. Kang K, Reilly SM, Karabacak V, Gangl MR, Fitzgerald K, Hatano B, Lee CH (2008) Adipocyte-derived Th2 cytokines and myeloid PPARdelta regulate macrophage polarization and insulin sensitivity. Cell Metab 7:485–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86

    Article  CAS  PubMed  Google Scholar 

  55. Meier CA, Chicheportiche R, Juge-Aubry CE, Dreyer MG, Dayer JM (2002) Regulation of the interleukin-1 receptor antagonist in THP-1 cells by ligands of the peroxisome proliferator-activated receptor gamma. Cytokine 18:320–328

    Article  CAS  PubMed  Google Scholar 

  56. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79–82

    Article  CAS  PubMed  Google Scholar 

  57. Chung SW, Kang BY, Kim SH, Pak YK, Cho D, Trinchieri G, Kim TS (2000) Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-gamma and nuclear factor-kappa B. J Biol Chem 275:32681–32687

    Article  CAS  PubMed  Google Scholar 

  58. Welch JS, Ricote M, Akiyama TE, Gonzalez FJ, Glass CK (2003) PPARgamma and PPARdelta negatively regulate specific subsets of lipopolysaccharide and IFN-gamma target genes in macrophages. Proc Natl Acad Sci U S A 100:6712–6717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ricote M, Glass CK (2007) PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta 1771:926–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437:759–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bouhlel MA, Derudas B, Rigamonti E, Dievart R, Brozek J, Haulon S, Zawadzki C, Jude B, Torpier G, Marx N, Staels B, Chinetti-Gbaguidi G (2007) PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 6:137–143

    Article  CAS  PubMed  Google Scholar 

  62. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Hevener AL, Olefsky JM, Reichart D, Nguyen MT, Bandyopadyhay G, Leung HY, Watt MJ, Benner C, Febbraio MA, Nguyen AK, Folian B, Subramaniam S, Gonzalez FJ, Glass CK, Ricote M (2007) Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117:1658–1669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chinetti G, Fruchart JC, Staels B (2001) Peroxisome proliferator-activated receptors (PPARs): nuclear receptors with functions in the vascular wall. Z Kardiol 90(Suppl 3):125–132

    PubMed  Google Scholar 

  65. Kiss M, Czimmerer Z, Nagy L (2013) The role of lipid-activated nuclear receptors in shaping macrophage and dendritic cell function: from physiology to pathology. J Allergy Clin Immunol 132:264–286

    Article  CAS  PubMed  Google Scholar 

  66. Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ (2002) Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 277:18793–18800

    Article  CAS  PubMed  Google Scholar 

  67. Fuentes L, Roszer T, Ricote M (2010) Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages. Mediat Inflamm 2010:219583

    Article  CAS  Google Scholar 

  68. Marathe C, Bradley MN, Hong C, Lopez F, Ruiz de Galarreta CM, Tontonoz P, Castrillo A (2006) The arginase II gene is an anti-inflammatory target of liver X receptor in macrophages. J Biol Chem 281:32197–32206

    Article  CAS  PubMed  Google Scholar 

  69. Ghisletti S, Huang W, Ogawa S, Pascual G, Lin ME, Willson TM, Rosenfeld MG, Glass CK (2007) Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma. Mol Cell 25:57–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Saklatvala J (2002) Glucocorticoids: do we know how they work? Arthritis Res 4:146–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ehrchen J, Steinmuller L, Barczyk K, Tenbrock K, Nacken W, Eisenacher M, Nordhues U, Sorg C, Sunderkotter C, Roth J (2007) Glucocorticoids induce differentiation of a specifically activated, anti-inflammatory subtype of human monocytes. Blood 109:1265–1274

    Article  CAS  PubMed  Google Scholar 

  72. Zizzo G, Cohen PL (2013) IL-17 stimulates differentiation of human anti-inflammatory macrophages and phagocytosis of apoptotic neutrophils in response to IL-10 and glucocorticoids. J Immunol 190:5237–5246

    Article  CAS  PubMed  Google Scholar 

  73. Hartman ZC, Osada T, Glass O, Yang XY, Lei GJ, Lyerly HK, Clay TM (2010) Ligand-independent toll-like receptor signals generated by ectopic overexpression of MyD88 generate local and systemic antitumor immunity. Cancer Res 70:7209–7220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Busillo JM, Cidlowski JA (2013) The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends Endocrinol Metab 24:109–119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee MJ, Pramyothin P, Karastergiou K, Fried SK (2014) Deconstructing the roles of glucocorticoids in adipose tissue biology and the development of central obesity. Biochim Biophys Acta 1842:473–481

    Article  CAS  PubMed  Google Scholar 

  76. Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 92:5510–5514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lewis JS, Lee JA, Underwood JC, Harris AL, Lewis CE (1999) Macrophage responses to hypoxia: relevance to disease mechanisms. J Leukoc Biol 66:889–900

    Article  CAS  PubMed  Google Scholar 

  78. O’Neill LA, Pearce EJ (2016) Immunometabolism governs dendritic cell and macrophage function. J Exp Med 213:15–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Nizet V, Johnson RS (2009) Interdependence of hypoxic and innate immune responses. Nat Rev Immunol 9:609–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fujisaka S, Usui I, Ikutani M, Aminuddin A, Takikawa A, Tsuneyama K, Mahmood A, Goda N, Nagai Y, Takatsu K, Tobe K (2013) Adipose tissue hypoxia induces inflammatory M1 polarity of macrophages in an HIF-1alpha-dependent and HIF-1alpha-independent manner in obese mice. Diabetologia 56:1403–1412

    Article  CAS  PubMed  Google Scholar 

  81. Takikawa A, Mahmood A, Nawaz A, Kado T, Okabe K, Yamamoto S, Aminuddin A, Senda S, Tsuneyama K, Ikutani M, Watanabe Y, Igarashi Y, Nagai Y, Takatsu K, Koizumi K, Imura J, Goda N, Sasahara M, Matsumoto M, Saeki K, Nakagawa T, Fujisaka S, Usui I, Tobe K (2016) HIF-1alpha in myeloid cells promotes adipose tissue remodeling toward insulin resistance. Diabetes 65:3649–3659

    Article  CAS  PubMed  Google Scholar 

  82. Treuter E, Fan R, Huang Z, Jakobsson T, Venteclef N (2017) Transcriptional repression in macrophages-basic mechanisms and alterations in metabolic inflammatory diseases. FEBS Lett 591:2959–2977

    Article  CAS  PubMed  Google Scholar 

  83. Glass CK, Ogawa S (2006) Combinatorial roles of nuclear receptors in inflammation and immunity. Nat Rev Immunol 6:44–55

    Article  PubMed  Google Scholar 

  84. Glass CK, Saijo K (2010) Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat Rev Immunol 10:365–376

    Article  CAS  PubMed  Google Scholar 

  85. Li P, Spann NJ, Kaikkonen MU, Lu M, Oh DY, Fox JN, Bandyopadhyay G, Talukdar S, Xu J, Lagakos WS, Patsouris D, Armando A, Quehenberger O, Dennis EA, Watkins SM, Auwerx J, Glass CK, Olefsky JM (2013) NCoR repression of LXRs restricts macrophage biosynthesis of insulin-sensitizing omega 3 fatty acids. Cell 155:200–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Chen X, Barozzi I, Termanini A, Prosperini E, Recchiuti A, Dalli J, Mietton F, Matteoli G, Hiebert S, Natoli G (2012) Requirement for the histone deacetylase Hdac3 for the inflammatory gene expression program in macrophages. Proc Natl Acad Sci U S A 109:E2865–E2874

    Article  PubMed  PubMed Central  Google Scholar 

  87. Mullican SE, Gaddis CA, Alenghat T, Nair MG, Giacomin PR, Everett LJ, Feng D, Steger DJ, Schug J, Artis D, Lazar MA (2011) Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev 25:2480–2488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Fan R, Toubal A, Goni S, Drareni K, Huang Z, Alzaid F, Ballaire R, Ancel P, Liang N, Damdimopoulos A, Hainault I, Soprani A, Aron-Wisnewsky J, Foufelle F, Lawrence T, Gautier JF, Venteclef N, Treuter E (2016) Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes. Nat Med 22:780–791

    Article  CAS  PubMed  Google Scholar 

  89. Drareni K, Ballaire R, Barilla S, Mathew MJ, Toubal A, Fan R, Liang N, Chollet C, Huang Z, Kondili M, Foufelle F, Soprani A, Roussel R, Gautier JF, Alzaid F, Treuter E, Venteclef N (2018) GPS2 deficiency triggers maladaptive white adipose tissue expansion in obesity via HIF1A activation. Cell Rep 24(2957–2971):e2956

    Google Scholar 

  90. Toubal A, Clement K, Fan R, Ancel P, Pelloux V, Rouault C, Veyrie N, Hartemann A, Treuter E, Venteclef N (2013) SMRT-GPS2 corepressor pathway dysregulation coincides with obesity-linked adipocyte inflammation. J Clin Invest 123:362–379

    Article  CAS  PubMed  Google Scholar 

  91. De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G (2007) The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell 130:1083–1094

    Article  CAS  PubMed  Google Scholar 

  92. De Santa F, Narang V, Yap ZH, Tusi BK, Burgold T, Austenaa L, Bucci G, Caganova M, Notarbartolo S, Casola S, Testa G, Sung WK, Wei CL, Natoli G (2009) Jmjd3 contributes to the control of gene expression in LPS-activated macrophages. EMBO J 28:3341–3352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kruidenier L, Chung CW, Cheng Z, Liddle J, Che K, Joberty G, Bantscheff M, Bountra C, Bridges A, Diallo H, Eberhard D, Hutchinson S, Jones E, Katso R, Leveridge M, Mander PK, Mosley J, Ramirez-Molina C, Rowland P, Schofield CJ, Sheppard RJ, Smith JE, Swales C, Tanner R, Thomas P, Tumber A, Drewes G, Oppermann U, Patel DJ, Lee K, Wilson DM (2012) A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488:404–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S (2010) The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol 11:936–944

    Article  CAS  PubMed  Google Scholar 

  95. Gallagher KA, Joshi A, Carson WF, Schaller M, Allen R, Mukerjee S, Kittan N, Feldman EL, Henke PK, Hogaboam C, Burant CF, Kunkel SL (2015) Epigenetic changes in bone marrow progenitor cells influence the inflammatory phenotype and alter wound healing in type 2 diabetes. Diabetes 64:1420–1430

    Article  CAS  PubMed  Google Scholar 

  96. Wahl S, Drong A, Lehne B, Loh M, Scott WR, Kunze S, Tsai PC, Ried JS, Zhang W, Yang Y, Tan S, Fiorito G, Franke L, Guarrera S, Kasela S, Kriebel J, Richmond RC, Adamo M, Afzal U, Ala-Korpela M, Albetti B, Ammerpohl O, Apperley JF, Beekman M, Bertazzi PA, Black SL, Blancher C, Bonder MJ, Brosch M, Carstensen-Kirberg M, de Craen AJ, de Lusignan S, Dehghan A, Elkalaawy M, Fischer K, Franco OH, Gaunt TR, Hampe J, Hashemi M, Isaacs A, Jenkinson A, Jha S, Kato N, Krogh V, Laffan M, Meisinger C, Meitinger T, Mok ZY, Motta V, Ng HK, Nikolakopoulou Z, Nteliopoulos G, Panico S, Pervjakova N, Prokisch H, Rathmann W, Roden M, Rota F, Rozario MA, Sandling JK, Schafmayer C, Schramm K, Siebert R, Slagboom PE, Soininen P, Stolk L, Strauch K, Tai ES, Tarantini L, Thorand B, Tigchelaar EF, Tumino R, Uitterlinden AG, van Duijn C, van Meurs JB, Vineis P, Wickremasinghe AR, Wijmenga C, Yang TP, Yuan W, Zhernakova A, Batterham RL, Smith GD, Deloukas P, Heijmans BT, Herder C, Hofman A, Lindgren CM, Milani L, van der Harst P, Peters A, Illig T, Relton CL, Waldenberger M, Jarvelin MR, Bollati V, Soong R, Spector TD, Scott J, McCarthy MI, Elliott P, Bell JT, Matullo G, Gieger C, Kooner JS, Grallert H, Chambers JC (2017) Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature 541:81–86

    Article  CAS  PubMed  Google Scholar 

  97. Dalmas E, Venteclef N, Caer C, Poitou C, Cremer I, Aron-Wisnewsky J, Lacroix-Desmazes S, Bayry J, Kaveri SV, Clement K, Andre S, Guerre-Millo M (2014) T cell-derived IL-22 amplifies IL-1beta-driven inflammation in human adipose tissue: relevance to obesity and type 2 diabetes. Diabetes 63:1966–1977

    Article  CAS  PubMed  Google Scholar 

  98. Caricilli AM, Nascimento PH, Pauli JR, Tsukumo DM, Velloso LA, Carvalheira JB, Saad MJ (2008) Inhibition of toll-like receptor 2 expression improves insulin sensitivity and signaling in muscle and white adipose tissue of mice fed a high-fat diet. J Endocrinol 199:399–406

    Article  CAS  PubMed  Google Scholar 

  99. Nackiewicz D, Dan M, He W, Kim R, Salmi A, Rutti S, Westwell-Roper C, Cunningham A, Speck M, Schuster-Klein C, Guardiola B, Maedler K, Ehses JA (2014) TLR2/6 and TLR4-activated macrophages contribute to islet inflammation and impair beta cell insulin gene expression via IL-1 and IL-6. Diabetologia 57:1645–1654

    Article  CAS  PubMed  Google Scholar 

  100. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araujo EP, Vassallo J, Curi R, Velloso LA, Saad MJ (2007) Loss-of-function mutation in toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 56:1986–1998

    Article  CAS  PubMed  Google Scholar 

  101. Brenachot X, Ramadori G, Ioris RM, Veyrat-Durebex C, Altirriba J, Aras E, Ljubicic S, Kohno D, Fabbiano S, Clement S, Goossens N, Trajkovski M, Harroch S, Negro F, Coppari R (2017) Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance. Nat Commun 8:1820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, Goforth MH, Subramanian V, Mukundan L, Ferrante AW, Chawla A (2008) Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 7:496–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Hedl M, Yan J, Abraham C (2016) IRF5 and IRF5 disease-risk variants increase glycolysis and human M1 macrophage polarization by regulating proximal signaling and Akt2 activation. Cell Rep 16:2442–2455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

N.V. was supported by grants from the French National Agency of Research (AngioSafe and PROVIDE), Region Ile de France (CORDDIM), Paris City (EMERGENCE), French and European Foundations for Diabetes (SFD and EFSD) and the European Union H2020 framework (ERC-EpiFAT).

Author information

Authors and Affiliations

  1. Cordeliers Research Centre, INSERM, Immunity and Metabolism in Diabetes Laboratory, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, F-75006, Paris, France

    Karima Drareni, Jean-François Gautier, Nicolas Venteclef & Fawaz Alzaid

  2. Lariboisière Hospital, AP-HP, Diabetology Department, University of Paris Diderot, Paris, France

    Jean-François Gautier

Authors
  1. Karima Drareni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean-François Gautier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicolas Venteclef
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fawaz Alzaid
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Nicolas Venteclef or Fawaz Alzaid.

Ethics declarations

Conflict of interest

The authors declare no competing financial interests.

Additional information

This article is a contribution to the special issue on Inflammation and Type 2 Diabetes - Guest Editor: Marc Y. Donath

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Drareni, K., Gautier, JF., Venteclef, N. et al. Transcriptional control of macrophage polarisation in type 2 diabetes. Semin Immunopathol 41, 515–529 (2019). https://doi.org/10.1007/s00281-019-00748-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-019-00748-1

Keywords

Search

Navigation