Macrophage/Monocyte-Endothelial Cell Crosstalk in Liver: Comparison
Please note this is a comparison between Version 2 by Vivi Li and Version 1 by Ines Coelho.

Inflammation is a hallmark of liver pathology, where macrophages and endothelial cells are pivotal players in promoting and sustaining disease progression. Understanding the drivers and mediators of these interactions will provide valuable information on what may contribute to liver resilience against disease. Here, we summarize the current knowledge on the role of macrophages and liver sinusoidal endothelial cells (LSEC) in homeostasis and liver pathology, with a particular focus on Trem-2 as a key mediator of these interactions.

Inflammation is a hallmark of liver pathology, where macrophages and endothelial cells are pivotal players in promoting and sustaining disease progression. Understanding the drivers and mediators of these interactions will provide valuable information on what may contribute to liver resilience against disease. In this entry, we summarize the current knowledge on the role of macrophages and liver sinusoidal endothelial cells (LSEC) in homeostasis and liver pathology, with a particular focus on Trem-2 as a key mediator of these interactions.

  • macrophages
  • endothelial cells
  • liver disease
  • cell interactions
  • Trem-2
Please wait, diff process is still running!

References

  1. Wynn, T.A.; Chawla, A.; Pollard, J.W. Macrophage biology in development, homeostasis and disease. Nature 2013, 496, 445–455.
  2. Okabe, Y.; Medzhitov, R. Tissue biology perspective on macrophages. Nat. Immunol. 2016, 17, 9–17.
  3. Furth, R.V.; Cohn, Z.A.; Hirsch, J.G.; Humphrey, J.H.; Spector, W.G.; Langevoort, H.L. The mononuclear phagocyte system: A new classification of macrophages, monocytes, and their precursor cells. Bull. World Health Organ. 1972, 45, 845–852.
  4. Bilzer, M.; Roggel, F.; Gerbes, A.L. Role of Kupffer cells in host defense and liver disease. Liver Int. 2006, 26, 1175–1186.
  5. Tacke, F. Targeting hepatic macrophages to treat liver diseases. J. Hepatol. 2017, 66, 1300–1312.
  6. Gordon, S.; Plüddemann, A. Tissue macrophages: Heterogeneity and functions. BMC Biol. 2017, 15, 1–18.
  7. Krenkel, O.; Tacke, F. Liver macrophages in tissue homeostasis and disease. Nat. Rev. Immunol. 2017, 17, 306–321.
  8. Scott, C.L.; Zheng, F.; De Baetselier, P.; Martens, L.; Saeys, Y.; De Prijck, S.; Lippens, S.; Abels, C.; Schoonooghe, S.; Raes, G.; et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat. Commun. 2016, 7, 10321.
  9. Yang, C.-Y.; Chen, J.-B.; Tsai, T.-F.; Tsai, Y.-C.; Tsai, C.-Y.; Liang, P.-H.; Hsu, T.-L.; Wu, C.-Y.; Netea, M.G.; Wong, C.-H.; et al. CLEC4F Is an Inducible C-Type Lectin in F4/80-Positive Cells and Is Involved in Alpha-Galactosylceramide Presentation in Liver. PLoS ONE 2013, 8, e65070.
  10. Lavin, Y.; Winter, D.; Blecher-Gonen, R.; David, E.; Keren-Shaul, H.; Merad, M.; Jung, S.; Amit, I. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell 2014, 159, 1312–1326.
  11. Davies, L.C.; Jenkins, S.J.; Allen, J.E.; Taylor, P.R. Tissue-resident macrophages. Nat. Immunol. 2013, 14, 986–995.
  12. Gordon, S.; Pl, A. Macrophage heterogeneity in tissues: Phenotypic diversity and functions. Immunol. Rev. 2014, 262, 36–55.
  13. Nairz, M.; Theurl, I.; Swirski, F.K.; Weiss, G. “Pumping iron”—How macrophages handle iron at the systemic, microenvironmental, and cellular levels. Pflügers Arch. Eur. J. Physiol. 2017, 469, 397–418.
  14. Scott, C.L.; Guilliams, M. The role of Kupffer cells in hepatic iron and lipid metabolism. J. Hepatol. 2018, 69, 1197–1199.
  15. Dixon, S.J.; Lemberg, K.M.; Lamprecht, M.R.; Skouta, R.; Zaitsev, E.M.; Gleason, C.E.; Patel, D.N.; Bauer, A.J.; Cantley, A.M.; Yang, W.S.; et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012, 149, 1060–1072.
  16. Bellentani, S. The epidemiology of non-alcoholic fatty liver disease. Liver Int. 2017, 37, 81–84.
  17. Devisscher, L.; Verhelst, X.; Colle, I.; Van Vlierberghe, H.; Geerts, A. The role of macrophages in obesity-driven chronic liver disease. J. Leukoc. Biol. 2016, 99, 693–698.
  18. Duarte, N.; Coelho, I.C.; Patarrão, R.S.; Almeida, J.I.; Penha-Gonçalves, C.; Macedo, M.P. How Inflammation Impinges on NAFLD: A Role for Kupffer Cells. Biomed Res. Int. 2015, 2015, 984578.
  19. Maher, J.J.; Leon, P.; Ryan, J.C. Beyond insulin resistance: Innate immunity in nonalcoholic steatohepatitis. Hepatology 2008, 48, 670–678.
  20. Remmerie, A.; Scott, C.L. Macrophages and lipid metabolism. Cell. Immunol. 2018, 330, 27–42.
  21. Leroux, A.; Ferrere, G.; Godie, V.; Cailleux, F.; Renoud, M.-L.; Gaudin, F.; Naveau, S.; Prévot, S.; Makhzami, S.; Perlemuter, G.; et al. Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis. J. Hepatol. 2012, 57, 141–149.
  22. Tosello-Trampont, A.C.; Landes, S.G.; Nguyen, V.; Novobrantseva, T.I.; Hahn, Y.S. Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production. J. Biol. Chem. 2012, 287, 40161–40172.
  23. Lanthier, N.; Molendi-Coste, O.; Horsmans, Y.; van Rooijen, N.; Cani, P.D.; Leclercq, I.A. Kupffer cell activation is a causal factor for hepatic insulin resistance. Am. J. Physiol. Liver Physiol. 2010, 298, G107–G116.
  24. Ni, Y.; Nagashimada, M.; Zhuge, F.; Zhan, L.; Nagata, N.; Tsutsui, A.; Nakanuma, Y.; Kaneko, S.; Ota, T. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with Vitamin, E. Sci. Rep. 2015, 5, 17192.
  25. Stienstra, R.; Saudale, F.; Duval, C.; Keshtkar, S.; Groener, J.E.M.; Van Rooijen, N.; Staels, B.; Kersten, S.; Müller, M. Kupffer cells promote hepatic steatosis via interleukin-1β-dependent suppression of peroxisome proliferator-activated receptor α activity. Hepatology 2010, 51, 511–522.
  26. Miura, K.; Yang, L.; van Rooijen, N.; Ohnishi, H.; Seki, E. Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2. Am. J. Physiol. Liver Physiol. 2012, 302, G1310–G1321.
  27. Huang, W.; Metlakunta, A.; Dedousis, N.; Zhang, P.; Sipula, I.; Dube, J.J.; Scott, D.K.; Doherty, R.M.O. Depletion of Liver Kupffer Cells Prevents the Development of Diet-Induced Hepatic Steatosis and Insulin Resistance. Diabetes 2010, 59, 347–357.
  28. Obstfeld, A.E.; Sugaru, E.; Thearle, M.; Francisco, A.; Gayet, C.; Ginsberg, H.N.; Ables, E.V.; Ferrante, A.W., Jr. C-C Chemokine Receptor 2 (CCR2) Regulates the Hepatic Recruitment of Myeloid Cells That Promote Obesity-Induced Hepatic Steatosis. Diabetes 2010, 59.
  29. Morinaga, H.; Mayoral, R.; Heinrichsdorff, J.; Osborn, O.; Franck, N.; Hah, N.; Walenta, E.; Bandyopadhyay, G.; Pessentheiner, A.R.; Chi, T.J.; et al. Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice. Diabetes 2015, 64, 1120–1130.
  30. Deng, Z.B.; Liu, Y.; Liu, C.; Xiang, X.; Wang, J.; Cheng, Z.; Shah, S.V.; Zhang, S.; Zhang, L.; Zhuang, X.; et al. Immature myeloid cells induced by a high-fat diet contribute to liver inflammation. Hepatology 2009, 50, 1412–1420.
  31. Krenkel, O.; Puengel, T.; Govaere, O.; Abdallah, A.T.; Mossanen, J.C.; Kohlhepp, M.; Liepelt, A.; Lefebvre, E.; Luedde, T.; Hellerbrand, C.; et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis. Hepatology 2018, 67, 1270–1283.
  32. Gadd, V.L.; Skoien, R.; Powell, E.E.; Fagan, K.J.; Winterford, C.; Horsfall, L.; Irvine, K.; Clouston, A.D. The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology 2014, 59, 1393–1405.
  33. Novo, E.; Cannito, S.; Paternostro, C.; Bocca, C.; Miglietta, A.; Parola, M. Cellular and molecular mechanisms in liver fibrogenesis. Arch. Biochem. Biophys. 2014, 548, 20–37.
  34. Pimpin, L.; Cortez-Pinto, H.; Negro, F.; Corbould, E.; Lazarus, J.V.; Webber, L.; Sheron, N. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. J. Hepatol. 2018, 69, 718–735.
  35. Ramachandran, P.; Iredale, J.P. Reversibility of liver fibrosis. Ann. Hepatol. 2009, 8, 283–291.
  36. Pellicoro, A.; Ramachandran, P.; Iredale, J.P.; Fallowfield, J. A Liver fibrosis and repair: Immune regulation of wound healing in a solid organ. Nat. Rev. Immunol. 2014, 14, 181–194.
  37. Tacke, F.; Zimmermann, H.W. Macrophage heterogeneity in liver injury and fibrosis. J. Hepatol. 2014, 60, 1090–1096.
  38. Loomba, R.; Lawitz, E.; Mantry, P.S.; Jayakumar, S.; Caldwell, S.H.; Arnold, H.; Diehl, A.M.; Djedjos, C.S.; Han, L.; Myers, R.P.; et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial. Hepatology 2018, 67, 549–559.
  39. Sanyal, A.; Vlad, R.; Harrison, S.; Abdelmalek, M.F.; Aithal, G.P.; Caballeria, J.; Francque, S.; Farrell, G.; Kowdley, K.V.; Craxi, A.; et al. Cenicriviroc versus Placebo for the Treatment of Nonalcoholic Steatohepatitis with Liver Fibrosis: Results from the Year 1 Primary Analysis of the Phase 2b. Hepatology 2015, 64, 1118–1119.
  40. Ding, B.; Nolan, D.J.; Butler, J.M.; James, D.; Babazadeh, A.O.; Rosenwaks, Z.; Mittal, V.; Kobayashi, H.; Shido, K.; Lyden, D.; et al. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature 2010, 468, 310–315.
  41. Wakabayashi, T.; Naito, H.; Suehiro, J.-i.; Lin, Y.; Kawaji, H.; Iba, T.; Kouno, T.; Ishikawa-Kato, S.; Furuno, M.; Takara, K.; et al. CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties. Cell Stem Cell 2018, 22, 384–397.e6.
  42. DeLeve, L.; Maretti-Mira, A. Liver Sinusoidal Endothelial Cell: An Update. Semin. Liver Dis. 2017, 37, 377–387.
  43. Wang, L.; Wang, X.; Wang, L.; Chiu, J.D.; Van De Ven, G.; Gaarde, W.A.; Deleve, L.D. Hepatic vascular endothelial growth factor regulates recruitment of rat liver sinusoidal endothelial cell progenitor cells. Gastroenterology 2012, 143, 1555–1563.e2.
  44. Harb, R.; Xie, G.; Lutzko, C.; Guo, Y.; Wang, X.; Hill, C.K.; Kanel, G.C.; DeLeve, L.D. Bone Marrow Progenitor Cells Repair Rat Hepatic Sinusoidal Endothelial Cells after Liver Injury. Gastroenterology 2009, 137, 704–712.
  45. Poisson, J.; Lemoinne, S.; Boulanger, C.; Durand, F.; Moreau, R.; Valla, D.; Rautou, P. Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J. Hepatol. 2017, 66, 212–227.
  46. Wisse, F.; Braet, E. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: A review. Comp. Hepatol. 2002, 12, 1–17.
  47. DeLeve, L.D.; Wang, X.; Guo, Y. Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence. Hepatology 2008, 48, 920–930.
  48. Sun, X.; Harris, E.N. New aspects of hepatic endothelial cells in physiology and nonalcoholic fatty liver disease. Am. J. Physiol. Physiol. 2020, 318, C1200–C1213.
  49. Miyao, M.; Kotani, H.; Ishida, T.; Kawai, C.; Manabe, S.; Abiru, H.; Tamaki, K. Pivotal role of liver sinusoidal endothelial cells in NAFLD / NASH progression. Lab. Investig. 2015, 95, 1130–1144.
  50. Peng, Q.; Zhang, Q.; Xiao, W.; Shao, M.; Fan, Q.; Zhang, H.; Zou, Y.; Li, X.; Xu, W.; Mo, Z.; et al. Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats. Biochem. Biophys. Res. Commun. 2014, 450, 685–691.
  51. Hammoutene, A.; Rautou, P. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J. Hepatol. 2019, 70, 1278–1291.
  52. Lefere, S.; Van de Velde, F.; Hoorens, A.; Raevens, S.; Van Campenhout, S.; Vandierendonck, A.; Neyt, S.; Vandeghinste, B.; Vanhove, C.; Debbaut, C.; et al. Angiopoietin-2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease. Hepatology 2019, 69, 1087–1104.
  53. Weston, C.J.; Shepherd, E.L.; Claridge, L.C.; Rantakari, P.; Curbishley, S.M.; Tomlinson, J.W.; Hubscher, S.G.; Reynolds, G.M.; Aalto, K.; Anstee, Q.M.; et al. Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis. J. Clin. Investig. 2015, 125, 501–520.
  54. Miyachi, Y.; Tsuchiya, K.; Komiya, C.; Shiba, K.; Shimazu, N.; Yamaguchi, S.; Deushi, M.; Osaka, M.; Inoue, K.; Sato, Y.; et al. Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Article Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance. Cell Rep. 2017, 18, 2766–2779.
  55. Wu, J.; Meng, Z.; Jiang, M.; Zhang, E.; Trippler, M.; Broering, R.; Bucchi, A.; Krux, F.; Dittmer, U.; Yang, D.; et al. Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific. Immunology 2010, 129, 363–374.
  56. Wu, L.Q.; Zhang, W.J.; Niu, J.X.; Ye, L.Y.; Yang, Z.H.; Grau, G.E.; Lou, J.N. Phenotypic and Functional Differences between Human Liver Cancer Endothelial Cells and Liver Sinusoidal Endothelial Cells. J. Vasc. Res. 2008, 45, 78–86.
  57. Ding, B.S.; Cao, Z.; Lis, R.; Nolan, D.J.; Guo, P.; Simons, M.; Penfold, M.E.; Shido, K.; Rabbany, S.Y.; Rafii, S. Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis. Nature 2014, 505, 97–102.
  58. Ribera, J.; Pauta, M.; Melgar-lesmes, P.; Córdoba, B.; Bosch, A.; Calvo, M.; Rodrigo-torres, D.; Sancho-bru, P.; Mira, A.; Jiménez, W.; et al. A small population of liver endothelial cells undergoes endothelial-to- mesenchymal transition in response to chronic liver injury. Liver Biliary Tract Physiol. Pathophysiol. 2017, 492–504.
  59. Lin, F.; Wang, N.; Zhang, T. The Role of Endothelial–Mesenchymal Transition in Development and Pathological Process. IUBMB Life 2012, 64, 717–723.
  60. Medici, D. Endothelial-Mesenchymal Transition in Regenerative Medicine. Stem Cells Int. 2016, 2016, 6962801.
  61. Zeisberg, E.M.; Tarnavski, O.; Zeisberg, M.; Dorfman, A.L.; McMullen, J.R.; Gustafsson, E.; Chandraker, A.; Yuan, X.; Pu, W.T.; Roberts, A.B.; et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat. Med. 2007, 13, 952–961.
  62. Mahler, G.J.; Farrar, E.J.; Butcher, J.T. Inflammatory Cytokines Promote Mesenchymal Transformation in Embryonic and Adult Valve Endothelial Cells. Arterioscler. Thromb. Vasc. Biol. 2013, 121–130.
  63. Pérez, L.; Muñoz-Durango, N.; Riedel, C.A.; Echeverría, C.; Kalergis, A.M.; Cabello-Verrugio, C.; Simon, F. Endothelial-to-mesenchymal transition: Cytokine-mediated pathways that determine endothelial fibrosis under inflammatory conditions. Cytokine Growth Factor Rev. 2017, 33, 41–54.
  64. Roh, Y.-S.; Seki, E. Chemokines and Chemokine Receptors in the Development of NAFLD. In Obesity, Fatty Liver and Liver Cancer; Springer: Berlin/Heidelberg, Germany, 2018; pp. 45–53.
  65. Kalucka, J.; Bierhansl, L.; Wielockx, B.; Carmeliet, P.; Eelen, G. Interaction of endothelial cells with macrophages—Linking molecular and metabolic signaling. Pflugers Arch. Eur. J. Physiol. 2017, 469, 473–483.
  66. Sakai, M.; Troutman, T.D.; Seidman, J.S.; Ouyang, Z.; Spann, N.J.; Abe, Y.; Ego, K.M.; Bruni, C.M.; Deng, Z.; Schlachetzki, J.C.M.; et al. Liver-Derived Signals Sequentially Reprogram Myeloid Enhancers to Initiate and Maintain Kupffer Cell Identity. Immunity 2019, 51, 655–670.e8.
  67. Bonnardel, J.; T’Jonck, W.; Gaublomme, D.; Browaeys, R.; Scott, C.L.; Martens, L.; Vanneste, B.; De Prijck, S.; Nedospasov, S.A.; Kremer, A.; et al. Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche. Immunity 2019, 51, 638–654.e9.
  68. Melgar-Lesmes, P.; Edelman, E.R. Monocyte-endothelial cell interactions in the regulation of vascular sprouting and liver regeneration in mouse. J. Hepatol. 2015, 63, 917–925.
  69. Ribatti, D.; Crivellato, E. “Sprouting angiogenesis”, a reappraisal. Dev. Biol. 2012, 372, 157–165.
  70. Lalor, P.F.; Tuncer, C.; Weston, C.; Martin-Santos, A.; Smith, D.J.; Adams, D.H. Vascular Adhesion Protein-1 as a Potential Therapeutic Target in Liver Disease. Ann. N. Y. Acad. Sci. 2007, 1110, 485–496.
  71. Vollmar, B.; Menger, M.D. The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair. Physiol. Rev. 2009, 89, 1269–1339.
  72. Spolarics, Z. Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid. J. Leukoc. Biol. 1998, 63, 534–541.
  73. Schubert, S.Y.; Benarroch, A.; Monter-Solans, J.; Edelman, E.R. Primary Monocytes Regulate Endothelial Cell Survival through Secretion of Angiopoietin-1 and Activation of Endothelial Tie2. Arterioscler. Thromb. Vasc. Biol. 2011, 31, 870–875.
  74. Schubert, S.Y.; Benarroch, A.; Ostvang, J.; Edelman, E.R. Regulation of Endothelial Cell Proliferation by Primary Monocytes. Arterioscler. Thromb. Vasc. Biol. 2008, 28, 97–104.
  75. Antonov, A.S.; Munn, D.H.; Kolodgie, F.D.; Virmani, R.; Gerrity, R.G. Aortic endothelial cells regulate proliferation of human monocytes in vitro via a mechanism synergistic with macrophage colony-stimulating factor. J. Clin. Investig. 1997, 99, 2867–2876.
  76. Li, H.; Zhou, Y.; Wang, H.; Zhang, M.; Qiu, P.; Zhang, M.; Zhang, R.; Zhao, Q.; Liu, J. Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis. Front. Immunol. 2020, 11, 1169.
  77. Seidman, J.S.; Troutman, T.D.; Sakai, M.; Gola, A.; Spann, N.J.; Bennett, H.; Bruni, C.M.; Ouyang, Z.; Li, R.Z.; Sun, X.; et al. Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis. Immunity 2020, 52, 1057–1074.e7.
  78. Helmke, A.; Casper, J.; Nordlohne, J.; David, S.; Haller, H.; Zeisberg, E.M.; von Vietinghoff, S. Endothelial-to-mesenchymal transition shapes the atherosclerotic plaque and modulates macrophage function. FASEB J. 2019, 33, 2278–2289.
  79. Wu, K.Q.; Muratore, C.S.; So, E.; Sun, C.; Dubielecka, P.M.; Reginato, A.M. M1 Macrophage e Induced Endothelial-to-Mesenchymal Transition Promotes Infantile Hemangioma Regression. Am. J. Pathol. 2017, 187, 2102–2111.
  80. Colonna, M. Trems in the immune system and beyond. Nat. Rev. Immunol. 2003, 3, 445–453.
  81. Ford, J.W.; McVicar, D.W. TREM and TREM-like receptors in inflammation and disease. Curr. Opin. Immunol. 2009, 21, 38–46.
  82. Colonna, M.; Wang, Y. TREM2 variants: New keys to decipher Alzheimer disease pathogenesis. Nat. Rev. Neurosci. 2016, 17, 201–207.
  83. Turnbull, I.R.; Gilfillan, S.; Cella, M.; Aoshi, T.; Miller, M.; Piccio, L.; Hernandez, M.; Colonna, M. Cutting edge: TREM-2 attenuates macrophage activation. J. Immunol. 2006, 177, 3520–3524.
  84. Kober, D.L.; Brett, T.J. TREM2-Ligand Interactions in Health and Disease. J. Mol. Biol. 2017, 429, 1607–1629.
  85. Park, M.; Yi, J.W.; Kim, E.M.; Yoon, I.J.; Lee, E.H.; Lee, H.Y.; Ji, K.Y.; Lee, K.H.; Jang, J.H.; Oh, S.S.; et al. Triggering receptor expressed on myeloid cells 2 (TREM2) promotes adipogenesis and diet-induced obesity. Diabetes 2015, 64, 117–127.
  86. Perugorria, M.J.; Esparza-Baquer, A.; Oakley, F.; Labiano, I.; Korosec, A.; Jais, A.; Mann, J.; Tiniakos, D.; Santos-Laso, A.; Arbelaiz, A.; et al. Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular damage. Gut 2019, 68, 533–546.
  87. Hsieh, C.L.; Koike, M.; Spusta, S.; Niemi, E.; Yenari, M.; Nakamura, C.M.; Seaman, W.E. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J. Neurochem. 2011, 109, 1144–1156.
  88. Takahashi, K.; Rochford, C.D.P.; Neumann, H. Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2. J. Exp. Med. 2005, 201, 647–657.
  89. Wang, Y.; Cella, M.; Mallinson, K.; Ulrich, J.D.; Young, K.L.; Robinette, M.L.; Gilfillan, S.; Krishnan, G.M.; Sudhakar, S.; Zinselmeyer, B.H.; et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 2015, 160, 1061–1071.
  90. Ulland, T.K.; Song, W.M.; Huang, S.C.C.; Ulrich, J.D.; Sergushichev, A.; Beatty, W.L.; Loboda, A.A.; Zhou, Y.; Cairns, N.J.; Kambal, A.; et al. TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease. Cell 2017, 170, 649–663.e13.
  91. Poliani, P.L.; Wang, Y.; Fontana, E.; Robinette, M.L.; Yamanishi, Y.; Gilfillan, S.; Colonna, M. TREM2 sustains microglial expansion during aging and response to demyelination. J. Clin. Investig. 2015, 125, 2161–2170.
  92. Esparza-Baquer, A.; Labiano, I.; Sharif, O.; Agirre-Lizaso, A.; Oakley, F.; Rodrigues, P.M.; Zhuravleva, E.; O’Rourke, C.J.; Hijona, E.; Jimenez-Agüero, R.; et al. TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms. Gut 2020.
  93. Xiong, X.; Kuang, H.; Ansari, S.; Liu, T.; Gong, J.; Wang, S.; Zhao, X.Y.; Ji, Y.; Li, C.; Guo, L.; et al. Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis. Mol. Cell 2019, 75, 644–660.e5.
  94. Xiong, X.; Wang, Q.; Wang, S.; Zhang, J.; Liu, T.; Guo, L.; Yu, Y.; Lin, J.D. Mapping the molecular signatures of diet-induced NASH and its regulation by the hepatokine Tsukushi. Mol. Metab. 2019, 20, 128–137.
  95. Ramachandran, P.; Dobie, R.; Wilson-Kanamori, J.R.; Dora, E.F.; Henderson, B.E.P.; Luu, N.T.; Portman, J.R.; Matchett, K.P.; Brice, M.; Marwick, J.A.; et al. Resolving the Fibrotic Niche of Human Liver Cirrhosis at Single-Cell Level; Springer: New York, NY, USA, 2019; Volume 575, ISBN 4158601916.
  96. Coelho, I.; Duarte, N.; Barros, A.; Macedo, M.P.; Penha-Gonçalves, C. Trem-2 promotes emergence of restorative macrophages and endothelial cells during recovery from hepatic tissue damage. Front. Immunol. 2021.
More
Video Production Service