CoChat
Sign Up
Cited by 41Immune cells in cancerLiver physiology and pathologyPhagocytosis and Immune Regulation

Hepatic Macrophage Responses in Inflammation, a Function of Plasticity, Heterogeneity or Both?

Open access
Zwicker, Christian, Bujko, Anna, Scott, Charlotte L.·2021·Frontiers in Immunology
DOI 10.3389/fimmu.2021.690813PMC PMC8220199
Open this paper in CoChat — free accountOpen PDF

Abstract

With the increasing availability and accessibility of single cell technologies, much attention has been given to delineating the specific populations of cells present in any given tissue. In recent years, hepatic macrophage heterogeneity has also begun to be examined using these strategies. While previously any macrophage in the liver was considered to be a Kupffer cell (KC), several studies have recently revealed the presence of distinct subsets of hepatic macrophages, including those distinct from KCs both under homeostatic and non-homeostatic conditions. This heterogeneity has brought the concept of macrophage plasticity into question. Are KCs really as plastic as once thought, being capable of responding efficiently and specifically to any given stimuli? Or are the differential responses observed from hepatic macrophages in distinct settings due to the presence of multiple subsets of these cells? With these questions in mind, here we examine what is currently understood regarding hepatic macrophage heterogeneity in mouse and human and examine the role of heterogeneity vs plasticity in regards to hepatic macrophage responses in settings of both pathogen-induced and sterile inflammation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2021.690813

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • LAMs are equivalent to scar-associated macrophages (SAM) in human MASH.

    “are equivalent to the scar-associated macrophages (SAM) in human MASH (6–8)”

    From Lipid-associated macrophages' promotion of fibrosis resolution during MASH regression requires TREM2 (2024) · cites this paper as [8]

    The Murine Hepatic Macrophages section says alignment of murine LAMs and human SAMs showed significant overlap, suggesting they could be equivalent populations. It does not establish equivalence as fact, and it describes human SAMs in fibrotic or cirrhotic livers rather than specifically in human MASH. Page numbers are unavailable in the supplied copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Macrophages are highly heterogeneous, reflected in both the co-existence of distinct macrophage populations within tissues and a degree of functional plasticity that allows individual macrophages to change their transcriptional and functional programs to adapt to diverse tissue environments and pathological contexts.

    “Macrophages, found throughout the body in health and disease, are highly heterogeneous. This is reflected in both the co-existence of distinct macrophage populations within tissues as well as a degree of functional plasticity that allows individual macrophages to change their transcriptional and functional programs to adapt to diverse tissue environments and pathological contexts (11, 12).”

    From Targeting macrophages in liver fibrosis (2026) · cites this paper as [12]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 93 · Cited by 41

Research works printed but not linked: 80

  1. [1]Underhill DM Gordon S Imhof BA Núñez G Bousso P. Élie Metchnikoff (1845-1916): Celebrating 100 Years of Cellular Immunology and Beyond. Nat Rev Immunol (2016) 16: 651–6. 10.1038/nri.2016.89 27477126 · DOI
  2. [2]Locati M Curtale G Mantovani A. Diversity, Mechanisms, and Significance of Macrophage Plasticity. Annu Rev Pathol Mech Dis (2019) 15: 1– 25. 10.1146/annurev-pathmechdis-012418-012718 PMC7176483 31530089 · DOI · Paper page
  3. [3]Aegerter H Kulikauskaite J Crotta S Patel H Kelly G Hessel EM. Influenza-Induced Monocyte-Derived Alveolar Macrophages Confer Prolonged Antibacterial Protection. Nat Immunol (2020) 21: 145–57. 10.1038/s41590-019-0568-x PMC6983324 31932810 · DOI
  4. [4]Remmerie A Martens L Thoné T Castoldi A Seurinck R Pavie B. Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct From Kupffer Cells in the Fatty Liver. Immunity (2020) 53: 641– 57.e14. 10.1016/j.immuni.2020.08.004 32888418 PMC7501731 · DOI · Paper page
  5. [5]Bain CC Mowat AM. Macrophages in Intestinal Homeostasis and Inflammation. Immunol Rev (2014) 260: 102–17. 10.1111/imr.12192 PMC4141699 24942685 · DOI
  6. [6]Remmerie A Martens L Scott CL. Macrophage Subsets in Obesity, Aligning the Liver and Adipose Tissue. Front Endocrinol (2020) 11: 633. 10.3389/fendo.2020.00259 PMC7201095 32411096 · DOI
  7. [7]Krenkel O Tacke F. Liver Macrophages in Tissue Homeostasis and Disease. Nat Rev Immunol (2017) 17: 306–21. 10.1038/nri.2017.11 28317925 · DOI · Paper page
  8. [8]Tacke F Zimmermann HW. Macrophage Heterogeneity in Liver Injury and Fibrosis. J Hepatol (2014) 60: 1090–6. 10.1016/j.jhep.2013.12.025 24412603 · DOI · Paper page
  9. [9]Mildner A Yona S Jung S. A Close Encounter of the Third Kind: Monocyte-Derived Cells. Adv Immunol (2013) 120: 69– 103. 10.1016/B978-0-12-417028-5.00003-X 24070381 · DOI
  10. [10]Varol C Mildner A Jung S. Macrophages: Development and Tissue Specialization. Annu Rev Immunol (2015) 33: 643–75. 10.1146/annurev-immunol-032414-112220 25861979 · DOI · Paper page
  11. [11]Gibbings SL Goyal R Desch AN Leach SM Prabagar M Atif SM. Transcriptome Analysis Highlights the Conserved Difference Between Embryonic and Postnatal-Derived Alveolar Macrophages. Blood (2015) 126: 1357–66. 10.1182/blood-2015-01-624809 PMC4566811 26232173 · DOI
  12. [12]Louwe PA Gomez LB Webster H Perona-Wright G Bain CC Forbes SJ. Recruited Macrophages That Colonize the Post-Inflammatory Peritoneal Niche Convert Into Functionally Divergent Resident Cells. Nat Commun (2021) 12: 1770. 10.1038/s41467-021-21778-0 33741914 PMC7979918 · DOI
  13. [13]Ydens E Amann L Asselbergh B Scott CL Martens L Sichien D. Profiling Peripheral Nerve Macrophages Reveals Two Macrophage Subsets With Distinct Localization, Transcriptome and Response to Injury. Nat Neurosci (2020) 23: 676–89. 10.1038/s41593-020-0618-6 PMC7611025 32284604 · DOI
  14. [14]Morgantini C Jager J Li X Levi L Azzimato V Sulen A. Liver Macrophages Regulate Systemic Metabolism Through Non-Inflammatory Factors. Nat Metab (2019) 1: 445–59. 10.1038/s42255-019-0044-9 32694874 · DOI
  15. [15]Zigmond E Samia-Grinberg S Pasmanik-Chor M Brazowski E Shibolet O Halpern Z. Infiltrating Monocyte-Derived Macrophages and Resident Kupffer Cells Display Different Ontogeny and Functions in Acute Liver Injury. J Immunol (2014) 193: 344–53. 10.4049/jimmunol.1400574 24890723 · DOI
  16. [16]Svedberg FR Brown SL Krauss MZ Campbell L Sharpe C Clausen M. The Lung Environment Controls Alveolar Macrophage Metabolism and Responsiveness in Type 2 Inflammation. Nat Immunol (2019) 20: 571–80. 10.1038/s41590-019-0352-y PMC8381729 30936493 · DOI
  17. [17]Ginhoux F Guilliams M. Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity (2016) 44: 439–49. 10.1016/j.immuni.2016.02.024 26982352 · DOI · Paper page
  18. [19]Perdiguero EG Geissmann F. The Development and Maintenance of Resident Macrophages. Nat Immunol (2016) 17: 2– 8. 10.1038/ni.3341 26681456 PMC4950995 · DOI
  19. [20]Guilliams M Scott CL. Does Niche Competition Determine the Origin of Tissue-Resident Macrophages? Nat Rev Immunol (2017) 128: 415. 10.1038/nri.2017.42 28461703 · DOI · Paper page
  20. [21]Sierro F Evrard M Rizzetto S Melino M Mitchell AJ Florido M. A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment. Immunity (2017) 47: 374– 88.e6. 10.1016/j.immuni.2017.07.018 28813662 · DOI
  21. [22]Scott CL Zheng F Baetselier PD Martens L Saeys Y Prijck SD. Bone Marrow-Derived Monocytes Give Rise to Self-Renewing and Fully Differentiated Kupffer Cells. Nat Commun (2016) 7: 10321. 10.1038/ncomms10321 26813785 PMC4737801 · DOI · Paper page
  22. [24]Seidman JS Troutman TD Sakai M Gola A Spann NJ Bennett H. Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis. Immunity (2020) 52(6): 1057–74.e7. 10.1016/j.immuni.2020.04.001 PMC7305990 32362324 · DOI · Paper page
  23. [25]Devisscher L Scott CL Lefere S Raevens S Bogaerts E Paridaens A. Non-Alcoholic Steatohepatitis Induces Transient Changes Within the Liver Macrophage Pool. Cell Immunol (2017) 322: 74– 83. 10.1016/j.cellimm.2017.10.006 29111158 · DOI
  24. [26]Beattie L Sawtell A Mann J Frame TCM Teal B de L. Rivera F. Bone Marrow-Derived and Resident Liver Macrophages Display Unique Transcriptomic Signatures But Similar Biological Functions. J Hepatol (2016) 65: 758–68. 10.1016/j.jhep.2016.05.037 PMC5028381 27262757 · DOI
  25. [27]MacParland SA Liu JC Ma X-Z Innes BT Bartczak AM Gage BK. Single Cell RNA Sequencing of Human Liver Reveals Distinct Intrahepatic Macrophage Populations. Nat Commun (2018) 9: 4383–21. 10.1038/s41467-018-06318-7 PMC6197289 30348985 · DOI · Paper page
  26. [28]Andrews TS Atif J Liu JC Perciani CT Ma X-Z Thoeni C. Single Cell, Single Nucleus and Spatial RNA Sequencing of the Human Liver Identifies Hepatic Stellate Cell and Cholangiocyte Heterogeneity. Biorxiv (2021). 10.1101/2021.03.27.436882 PMC8948611 34792289 · DOI
  27. [29]Aizarani N Saviano A Sagar Mailly L Durand S Herman JS. A Human Liver Cell Atlas Reveals Heterogeneity and Epithelial Progenitors. Nature (2019) 572: 199– 204. 10.1038/s41586-019-1373-2 31292543 PMC6687507 · DOI · Paper page
  28. [30]Ramachandran P Dobie R Wilson-Kanamori JR Dora EF Henderson BEP Luu NT. Resolving the Fibrotic Niche of Human Liver Cirrhosis at Single-Cell Level. Nature (2019) 38: 2– 29. 10.1101/766113 PMC6876711 31597160 · DOI
  29. [31]Wu X Hollingshead N Roberto J Knupp A Kenerson H Chen A. Human Liver Macrophage Subsets Defined by CD32. Front Immunol (2020) 11: 2108. 10.3389/fimmu.2020.02108 33101269 PMC7546764 · DOI
  30. [34]Wake K. Karl Wilhelm Kupffer And His Contributions to Modern Hepatology. Comp Hepatol (2004) 3: S2. 10.1186/1476-5926-2-S1-S2 14960154 PMC2410225 · DOI
  31. [35]Yang C-Y Chen J-B Tsai T-F Tsai C-Y Hsieh S-L. 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(6): e65070. 10.1371/journal.pone.0065070 23762286 PMC3675125 · DOI
  32. [37]Gola A Dorrington MG Speranza E Sala C Shih RM Radtke AJ. Commensal-Driven Immune Zonation of the Liver Promotes Host Defence. Nature (2021) 589: 131–6. 10.1038/s41586-020-2977-2 PMC8691525 33239787 · DOI
  33. [38]Graubardt N Vugman M Mouhadeb O Caliari G Pasmanik-Chor M Reuveni D. Ly6chi Monocytes and Their Macrophage Descendants Regulate Neutrophil Function and Clearance in Acetaminophen-Induced Liver Injury. Front Immunol (2017) 8: 626. 10.3389/fimmu.2017.00626 28620383 PMC5451509 · DOI
  34. [39]Rolot M Dougall AM Javaux J Lallemand F Machiels B Martinive P. Recruitment of Hepatic Macrophages From Monocytes is Independent of IL-4Rα But is Associated With Ablation of Resident Macrophages in Schistosomiasis. Eur J Immunol (2019) 49: 1067–81. 10.1002/eji.201847796 30919955 · DOI
  35. [40]Theurl I Hilgendorf I Nairz M Tymoszuk P Haschka D Asshoff M. On-Demand Erythrocyte Disposal and Iron Recycling Requires Transient Macrophages in the Liver. Nat Med (2016) 22: 945–51. 10.1038/nm.4146 PMC4957133 27428900 · DOI · Paper page
  36. [42]Guilliams M Thierry GR Bonnardel J Bajénoff M. Establishment and Maintenance of the Macrophage Niche. Immunity (2020) 52: 434–51. 10.1016/j.immuni.2020.02.015 32187515 · DOI · Paper page
  37. [43]Liu Z Gu Y Chakarov S Bleriot C Kwok I Chen X. Fate Mapping Via Ms4a3-Expression History Traces Monocyte-Derived Cells. Cell (2019) 178: 1509– 25.e19. 10.1016/j.cell.2019.08.009 31491389 · DOI · Paper page
  38. [44]Dutertre C-A Becht E Irac SE Khalilnezhad A Narang V Khalilnezhad S. Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells. Immunity (2019) 51: 573– 89.e8. 10.1016/j.immuni.2019.08.008 31474513 · DOI
  39. [45]See P Dutertre C-A Chen J Günther P McGovern N Irac SE. Mapping the Human DC Lineage Through the Integration of High-Dimensional Techniques. Science (New York NY) (2017) 356: eaag3009. 10.1126/science.aag3009 PMC7611082 28473638 · DOI
  40. [47]Gaskell H Ge X Nieto N. High-Mobility Group Box-1 and Liver Disease. Hepatol Commun (2018) 2: 1005–20. 10.1002/hep4.1223 PMC6128227 30202816 · DOI
  41. [49]Ballesteros I Rubio-Ponce A Genua M Lusito E Kwok I Fernández-Calvo G. Co-Option of Neutrophil Fates by Tissue Environments. Cell (2020) 183: 1282– 97.e18. 10.1016/j.cell.2020.10.003 33098771 · DOI
  42. [50]Scott CL T’Jonck W Martens L Todorov H Sichien D Soen B. The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages. Immunity (2018) 49(2): 312–25.e5. 10.1016/j.immuni.2018.07.004 PMC6104815 30076102 · DOI
  43. [51]Crispe IN. The Liver as a Lymphoid Organ. Annu Rev Immunol (2009) 27: 147–63. 10.1146/annurev.immunol.021908.132629 19302037 · DOI · Paper page
  44. [52]Jenne CN Kubes P. Immune Surveillance by the Liver. Nat Immunol (2013) 14: 996– 1006. 10.1038/ni.2691 24048121 · DOI · Paper page
  45. [53]Yan J Li S Li S. The Role of the Liver in Sepsis. Int Rev Immunol (2014) 33: 498– 510. 10.3109/08830185.2014.889129 24611785 PMC4160418 · DOI
  46. [54]Woolbright BL Jaeschke H. The Impact of Sterile Inflammation in Acute Liver Injury. J Clin Transl Res (2017) 3(S1): 170–88. 10.18053/jctres.03.2017S1.003 PMC5488807 28670626 · DOI
  47. [55]Knolle P Schlaak J Uhrig A Kempf P H. M. zum Büschenfelde K Gerken G. Human Kupffer Cells Secrete IL-10 in Response to Lipopolysaccharide (LPS) Challenge. J Hepatol (1995) 22: 226–9. 10.1016/0168-8278(95)80433-1 7790711 · DOI
  48. [56]Deng M Scott MJ Loughran P Gibson G Sodhi C Watkins S. Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type–Specific Functions of TLR4 During Sepsis. J Immunol (2013) 190: 5152–60. 10.4049/jimmunol.1300496 PMC3644895 23562812 · DOI
  49. [57]Lee W-Y Moriarty TJ Wong CHY Zhou H Strieter RM van Rooijen N. An Intravascular Immune Response to Borrelia Burgdorferi Involves Kupffer Cells and iNKT Cells. Nat Immunol (2010) 11: 295– 302. 10.1038/ni.1855 20228796 PMC5114121 · DOI
  50. [58]Canbay A Feldstein AE Higuchi H Werneburg N Grambihler A Bronk SF. Kupffer Cell Engulfment of Apoptotic Bodies Stimulates Death Ligand and Cytokine Expression. Hepatology (2003) 38: 1188–98. 10.1053/jhep.2003.50472 14578857 · DOI
  51. [60]Sitia G Iannacone M Aiolfi R Isogawa M van Rooijen N Scozzesi C. Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis. PloS Pathog (2011) 7: e1002061. 10.1371/journal.ppat.1002061 21655107 PMC3107209 · DOI
  52. [61]Tian Y Kuo C Akbari O Ou JJ. Maternal-Derived Hepatitis B Virus E Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence After Vertical Transmission. Immunity (2016) 44: 1204–14. 10.1016/j.immuni.2016.04.008 PMC4871724 27156385 · DOI
  53. [62]Ginhoux F Bleriot C Lecuit M. Dying for a Cause: Regulated Necrosis of Tissue-Resident Macrophages Upon Infection. Trends Immunol (2017) 38: 693–5. 10.1016/j.it.2017.05.009 28642066 · DOI
  54. [63]Guillot A Tacke F. Liver Macrophages: Old Dogmas and New Insights. Hepatol Commun (2019) 3: 730–43. 10.1002/hep4.1356 PMC6545867 31168508 · DOI
  55. [64]Holt MP Cheng L Ju C. Identification and Characterization of Infiltrating Macrophages in Acetaminophen-Induced Liver Injury. J Leukoc Biol (2008) 84: 1410–21. 10.1189/jlb.0308173 PMC2614594 18713872 · DOI
  56. [65]Dambach DM Watson LM Gray KR Durham SK Laskin DL. Role of CCR2 in Macrophage Migration Into the Liver During Acetaminophen-Induced Hepatotoxicity in the Mouse. Hepatology (2002) 35: 1093–103. 10.1053/jhep.2002.33162 11981759 · DOI · Paper page
  57. [66]You Q Holt M Yin H Li G Hu C-J Ju C. Role of Hepatic Resident and Infiltrating Macrophages in Liver Repair After Acute Injury. Biochem Pharmacol (2013) 86: 836–43. 10.1016/j.bcp.2013.07.006 PMC3863645 23876342 · DOI
  58. [67]Emmanuilidis K Weighardt H Maier S Gerauer K Fleischmann T Zheng XX. Critical Role of Kupffer Cell-Derived IL-10 for Host Defense in Septic Peritonitis. J Immunol (2001) 167: 3919–27. 10.4049/jimmunol.167.7.3919 11564810 · DOI
  59. [68]Breous E Somanathan S Vandenberghe LH Wilson JM. Hepatic Regulatory T Cells and Kupffer Cells Are Crucial Mediators of Systemic T Cell Tolerance to Antigens Targeting Murine Liver. Hepatology (2009) 50: 612–21. 10.1002/hep.23043 PMC4380144 19575456 · DOI · Paper page
  60. [69]Ju C Reilly TP Bourdi M Radonovich MF Brady JN George JW. Protective Role of Kupffer Cells in Acetaminophen-Induced Hepatic Injury in Mice. Chem Res Toxicol (2002) 15: 1504–13. 10.1021/tx0255976 12482232 · DOI
  61. [70]Campion SN Johnson R Aleksunes LM Goedken MJ van Rooijen N Scheffer GL. Hepatic Mrp4 Induction Following Acetaminophen Exposure is Dependent on Kupffer Cell Function. Am J Physiol Gastrointest Liver Physiol (2008) 295: G294–304. 10.1152/ajpgi.00541.2007 PMC2519859 18556419 · DOI
  62. [72]Kolodziejczyk AA Federici S Zmora N Mohapatra G Dori-Bachash M Hornstein S. Acute Liver Failure is Regulated by MYC- and Microbiome-Dependent Programs. Nat Med (2020) 26: 1899–911. 10.1038/s41591-020-1102-2 33106666 · DOI
  63. [73]Davies LC Rosas M Jenkins SJ Liao C-T Scurr MJ Brombacher F. Distinct Bone Marrow-Derived and Tissue-Resident Macrophage Lineages Proliferate at Key Stages During Inflammation. Nat Commun (2013) 4: 1886. 10.1038/ncomms2877 23695680 PMC3842019 · DOI
  64. [74]Gautier EL Ivanov S Lesnik P Randolph GJ. Local Apoptosis Mediates Clearance of Macrophages From Resolving Inflammation in Mice. Blood (2013) 122: 2714–22. 10.1182/blood-2013-01-478206 PMC3795463 23974197 · DOI
  65. [75]Xiong X Kuang H Ansari S Liu T Gong J Wang S. Landscape of Intercellular Crosstalk in Healthy and NASH Liver Revealed by Single-Cell Secretome Gene Analysis. Mol Cell (2019) 75: 644– 660.e5. 10.1016/j.molcel.2019.07.028 31398325 PMC7262680 · DOI · Paper page
  66. [76]Krenkel O Hundertmark J Abdallah AT Kohlhepp M Puengel T Roth T. Myeloid Cells in Liver and Bone Marrow Acquire a Functionally Distinct Inflammatory Phenotype During Obesity-Related Steatohepatitis. Gut (2020) 69: 551–63. 10.1136/gutjnl-2019-318382 31076404 · DOI · Paper page
  67. [77]Schneider KM Elfers C Ghallab A Schneider CV Galvez EJC Mohs A. Intestinal Dysbiosis Amplifies Acetaminophen-Induced Acute Liver Injury. Cell Mol Gastroenterol Hepatol (2021) 11: 909–33. 10.1016/j.jcmgh.2020.11.002 PMC7900526 33189892 · DOI · Paper page
  68. [78]Gong S Lan T Zeng L Luo H Yang X Li N. Gut Microbiota Mediates Diurnal Variation of Acetaminophen Induced Acute Liver Injury in Mice. J Hepatol (2018) 69: 51–9. 10.1016/j.jhep.2018.02.024 PMC6365016 29524531 · DOI
  69. [79]McDonald B Zucoloto AZ Yu I-L Burkhard R Brown K Geuking MB. Programing of an Intravascular Immune Firewall by the Gut Microbiota Protects Against Pathogen Dissemination During Infection. Cell Host Microbe (2020) 28: 660– 8.e4. 10.1016/j.chom.2020.07.014 32810440 · DOI
  70. [80]David BA Rezende RM Antunes MM Santos MM Lopes MAF Diniz AB. Combination of Mass Cytometry and Imaging Analysis Reveals Origin, Location, and Functional Repopulation Of Liver Myeloid Cells in Mice. Gastroenterology (2016) 151: 1176–91. 10.1053/j.gastro.2016.08.024 27569723 · DOI
  71. [81]Borst K Frenz T Spanier J Tegtmeyer P-K Chhatbar C Skerra J. Type I Interferon Receptor Signaling Delays Kupffer Cell Replenishment During Acute Fulminant Viral Hepatitis. J Hepatol (2018) 68: 682–90. 10.1016/j.jhep.2017.11.029 29274730 · DOI
  72. [82]Anthony BJ Ramm GA McManus DP. Role of Resident Liver Cells in the Pathogenesis of Schistosomiasis. Trends Parasitol (2012) 28: 572–9. 10.1016/j.pt.2012.09.005 23099112 · DOI
  73. [83]Wilson MS Mentink-Kane MM Pesce JT Ramalingam TR Thompson R Wynn TA. Immunopathology of Schistosomiasis. Immunol Cell Biol (2007) 85: 148–54. 10.1038/sj.icb.7100014 PMC3437548 17160074 · DOI
  74. [84]Barron L Wynn TA. Macrophage Activation Governs Schistosomiasis-Induced Inflammation and Fibrosis. Eur J Immunol (2011) 41: 2509–14. 10.1002/eji.201141869 PMC3408543 21952807 · DOI
  75. [85]Jenkins SJ Ruckerl D Cook PC Jones LH Finkelman FD van Rooijen N. Local Macrophage Proliferation, Rather Than Recruitment From the Blood, is a Signature of TH2 Inflammation. Science (2011) 332: 1284–8. 10.1126/science.1204351 PMC3128495 21566158 · DOI
  76. [86]Jenkins SJ Ruckerl D Thomas GD Hewitson JP Duncan S Brombacher F. IL-4 Directly Signals Tissue-Resident Macrophages to Proliferate Beyond Homeostatic Levels Controlled by CSF-1IL-4 Drives Macrophage Proliferation. J Exp Med (2013) 210: 2477–91. 10.1084/jem.20121999 PMC3804948 24101381 · DOI
  77. [87]Girgis NM Gundra UM Ward LN Cabrera M Frevert U Loke P. Ly6chigh Monocytes Become Alternatively Activated Macrophages in Schistosome Granulomas With Help From CD4+ Cells. PloS Pathog (2014) 10: e1004080. 10.1371/journal.ppat.1004080 24967715 PMC4072804 · DOI
  78. [88]Nascimento M Huang SC Smith A Everts B Lam W Bassity E. Ly6chi Monocyte Recruitment Is Responsible for Th2 Associated Host-Protective Macrophage Accumulation in Liver Inflammation Due to Schistosomiasis. PloS Pathog (2014) 10: e1004282. 10.1371/journal.ppat.1004282 25144366 PMC4140849 · DOI
  79. [90]Itoh M Suganami T Kato H Kanai S Shirakawa I Sakai T. CD11c+ Resident Macrophages Drive Hepatocyte Death-Triggered Liver Fibrosis in a Murine Model of Nonalcoholic Steatohepatitis. JCI Insight (2017) 2: e92902. 10.1172/jci.insight.92902 PMC5752377 29202448 · DOI
  80. [92]Satoh T Nakagawa K Sugihara F Kuwahara R Ashihara M Yamane F. Identification of an Atypical Monocyte and Committed Progenitor Involved in Fibrosis. Nature (2017) 541: 96– 101. 10.1038/nature20611 28002407 · DOI · Paper page

Authors
Zwicker, C., Bujko, A., & Scott, C. L.
Affiliations
  • Vlaams Instituut voor Biotechnologie (BE)
  • University of Limerick (IE)
Corresponding author
Scott, Charlotte L.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2021-06-09
Volume
12
Pages
690813-690813
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2021.690813
PMC
PMC8220199
OpenAlex
W3167309162
Cited by
41
References
93
Citations by year
2026: 7 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 3
FWCI
0.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Limerick Institutional Repository (University of Limerick) (acceptedVersion, other-oa)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
Funders
  • FP7 Ideas: European Research Council (851908)
  • H2020 Marie Skłodowska-Curie Actions
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
hepatic macrophages, Kupffer cells, macrophage heterogeneity, macrophage plasticity, liver inflammation, sterile inflammation, single-cell analysis
MeSH terms
Animals, Humans, Inflammation, Liver, Macrophages

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review