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| 1 | Hepatic macrophages in liver homeostasis and diseasesdiversity,plasticity and therapeutic opportunities显示文摘Macrophages,which are key cellular components of the liver,have emerged as essential players in the maintenance of hepatic homeostasis and in injury and repair processes in acute and chronic liver diseases.Upon liver injury,resident Kupffer cells(KCs)sense disturbances in homeostasis,interact with hepatic cell populations and release chemokines to recruit circulating leukocytes,including monocytes,which subsequently differentiate into monocyte-derived macrophages(MoMφs)in the liver.Both KCs and MoMφs contribute to both the progression and resolution of tissue inflammation and injury in various liver diseases.The diversity of hepatic macrophage subsets and their plasticity explain their different functional responses in distinct liver diseases.In this review,we highlight novel findings regarding the origins and functions of hepatic macrophages and discuss the potential of targeting macrophages as a therapeutic strategy for liver disease. | Yankai Wen Joeri Lambrecht Cynthia Ju Frank Tacke | 2021 | Cellular & Molecular Immunology2021，18，1： | 21 |
| 2 | Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages显示文摘How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated.Here,we perform single-cell deep-immune profiling of bronchoalveolar lavage(BAL)samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung.We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them.In mild COVID-19,CD8^(+)resident-memory(TRM)and CD4^(+)T-helper-17(T_(H17))cells undergo active(presumably antigen-driven)expansion towards the end of the trajectory,and are characterized by good effector functions,while in critical COVID-19 they remain more naïve.Vice versa,CD4^(+)T-cells with T-helper-1 characteristics(TH1-like)and CD8^(+)T-cells expressing exhaustion markers(T_(EX)-like)are enriched halfway their trajectories in mild COVID-19,where they also exhibit good effector functions,while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories.Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19,while alveolar macrophages,otherwise characterized by anti-inflammatory and antigen-presenting characteristics,are depleted.In critical COVID-19,monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity.Finally,viral RNA-tracking reveals infected lung epithelial cells,and a significant proportion of neutrophils and macrophages that are involved in viral clearance. | Els Wauters Pierre Van Mol Abhishek Dinkarnath Garg Sander Jansen Yannick Van Herck Lore Vanderbeke Ayse Bassez Bram Boeckx Bert Malengier-Devlies Anna Timmerman Thomas Van Brussel Tina Van Buyten Rogier Schepers Elisabeth Heylen Dieter Dauwe Christophe Dooms Jan Gunst Greet Hermans Philippe Meersseman Dries Testelmans Jonas Yserbyt Sabine Tejpar Walter De Wever Patrick Matthys CONTAGIOUS collaborators Johan Neyts Joost Wauters Junbin Qian Diether Lambrechts | 2021 | Cell Research2021，31，3： | 11 |
| 3 | A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling显示文摘The stromal compartment of the tumor microenvironment consists of a heterogeneous set of tissue-resident and tumor-infiltrating cells,which are profoundly moulded by cancer cells.An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs.Here,we profile 233,591 single cells from patients with lung,colorectal,ovary and breast cancer(n=36)and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies.We identify 68 stromal cell populations,of which 46 are shared between cancer types and 22 are unique.We also characterise each population phenotypically by highlighting its marker genes,transcription factors,metabolic activities and tissue-specific expression differences.Resident cell types are characterised by substantial tissue specificity,while tumor-infiltrating cell types are largely shared across cancer types.Finally,by applying the blueprint to melanoma tumors treated with checkpoint immunotherapy and identifying a naive CD4+T-cell phenotype predictive of response to checkpoint immunotherapy,we illustrate how it can serve as a guide to interpret scRNA-seq data.In conclusion,by providing a comprehensive blueprint through an interactive web server,we generate the first panoramic view on the shared complexity of stromal cells in different cancers. | Junbin Qian Siel Olbrecht Bram Boeckx Hanne Vos Damya Laoui Emre Etlioglu Els Wauters Valentina Pomella Sara Verbandt Pieter Busschaert Ayse Bassez Amelie Franken Marlies Vanden Bempt Jieyi Xiong Birgit Weynand Yannick van Herck Asier Antoranz Francesca Maria Bosisio Bernard Thienpont Giuseppe Floris Ignace Vergote Ann Smeets Sabine Tejpar Diether Lambrechts | 2020 | Cell Research2020，30，9： | 11 |
| 4 | Iron increases HMOX1 and decreases hepatitis C viral expression in HCV-expressing cells显示文摘AIM:To investigate effects of iron on oxidative stress, heme oxygenase-1(HMOX1)and hepatitis C viral(HCV) expression in human hepatoma cells stably expressing HCV proteins. METHODS:Effects of iron on oxidative stress,HMOX1, and HCV expression were assessed in CON1 cells. Measurements included mRNA by quantitative reverse transcription-polymerase chain reaction,and protein levels by Western blots. RESULTS:Iron,in the form of ferric nitrilotriacetate,increased oxidative stress and up-regulated HMOX1 gene expression.Iron did not affect mRNA or protein levels of Bach1,a repressor of HMOX1.Silencing the up-regulation of HMOX1 nuclear factor-erythroid 2-related factor 2(Nrf2)by Nrf2-siRNA decreased FeNTA-mediated up-regulation of HMOX1 mRNA levels.These iron effects were completely blocked by deferoxamine(DFO).Iron also significantly decreased levels of HCV core mRNA and protein by 80%-90%, nonstructural 5A mRNA by 90%and protein by about 50%in the Con1 full length HCV replicon cells, whereas DFO increased them. CONCLUSION:Excess iron up-regulates HMOX1 and down-regulates HCV gene expression in hepatoma cells.This probably mitigates liver injury caused by combined iron overload and HCV infection. | Wei-Hong Hou Lisa Rossi Ying Shan Jian-Yu Zheng Richard W Lambrecht Herbert L Bonkovsky | 2009 | World Journal of Gastroenterology2009，15，36： | 5 |
| 5 | Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis显示文摘 | Herbert L Bonkovsky Qaiser Jawaid Kristina Tortorelli Paula LeClair Joseph Cobb Richard W Lambrecht Barbara F Banner | 1999 | Journal of Hepatology1999，，3： | 2 |
| 6 | Reciprocal Effects of Micro-RNA-122 on Expression of Heme Oxygenase-1 and Hepatitis C Virus Genes in Human Hepatocytes显示文摘 | Ying Shan Jianyu Zheng Richard W. Lambrecht Herbert L. Bonkovsky | 2007 | Gastroenterology2007，，4： | 2 |
| 7 | Role of Bachl and Nrf2 in up-regulation of the heme oxygenase- 1 gene by cobalt protoporphyrin 显示文摘 | Shan Y Lambrecht RW Donohue SE | 2006 | FASEB J2006，20，14： | 1 |
| 8 | The molecular structure of hepatoproliferin: a regeneration factor from rat hepatocytes显示文摘 | Oosthuizen M J Lambrechts H | 1997 | FASEB J1997，11，： | 1 |
| 9 | Optical-absorption bands in the 1-3 eV range in n-type SiC polytypes 显示文摘 | LIMPIJUMNONG S LAMBRECHT W R L RASHKEEV S N | 1998 | Physical Review B1998，57，12： | 1 |
| 10 | Allergen-Induced changes in bone-marrow progenitor and airway dendritic cells in sensitized rats显示文摘 | Lambrecht BN Carro-Muino I Vermaelenk | 1999 | Am J Respir Cell Mol Biol1999，20，6： | 1 |
| 11 | Transfer function analysis of forecasting induced bullwhip in supply chain显示文摘 | Dejonckeere J Disney S M Lambrecht M R | 2002 | International Journal of Production Economics2002，78，2： | 1 |
| 12 | Utilization of phytate by some yeast显示文摘 | LAMBRECHTS C BOZE H | 1992 | Biotechnology Letters1992，4，1： | 1 |
| 13 | Influence of dif- ferent chemical elements on irradiation-induced hardening embrittlement of RPV steels 显示文摘 | Lambrecht M Malerba L Almazouzi A | 2008 | Journal of Nuclear Ma- terials2008，378，3： | 1 |
| 14 | Deep venous throm- bosis in gynecological oncology: incidence and clinical symptoms study 显示文摘 | Santoso J T Evans L Lambrecht L | 2009 | Eur J Obstet Gynecol Reprod Biol2009，144，2： | 1 |
| 15 | Vitamin D status at breast cancer diagnosis: correlation with tumor characteristics, disease outcome, and genetic determinants of vitamin D insufficiency显示文摘 | Hatse S Lambrechts D Verstuyf A | 2012 | Carcinogenesis2012，33，： | 1 |
| 16 | Anopheles gambiae immune responses to Sephadex beads:involvement of anti-Plasmodium factors in regulating melanization显示文摘 | Warr E Lambrechts L Koella JC | | 0，，10： | 1 |
| 17 | Isolation and characterization of endophytic colonizing bacteria from agro- nomic crops and prairie plants显示文摘 | ZINNIEL D K LAMBRECHT P HARRIS N B | 2002 | Applied and Environmental Microbiologyaem2002，68，： | 1 |
| 18 | Treatment of severe thallium intoxication显示文摘 | Malbrain ML Lambrecht GL Zandijk E | 1997 | J Toxicol Clin Toxicol1997，35，1： | 1 |
| 19 | VEGF at the neurovascular interface:therapeutic implications for motor neuron disease显示文摘 | | 2006 | Biochim Biophys Acta2006，1762，1112： | 1 |
| 20 | Sequencing of the coding exons of the LRP1 and LDLR genes on individual DNA samples reveals novel mutations in both genes显示文摘 | LEUVEN V F THIRY E LAMBRECHTS M | 2001 | Atherosclerosis2001，154，3： | 1 |
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