Article
Engineering, Biomedical
Liam M. Casey, Kevin R. Hughes, Michael N. Saunders, Stephen D. Miller, Ryan M. Pearson, Lonnie D. Shea
Summary: The delivery of disease-relevant antigens by polymeric nanoparticles has shown to induce immune tolerance in various disorders. This study investigated the contribution of liver sinusoidal endothelial cells and Kupffer cells in nanoparticle-induced tolerance in a mouse model of multiple sclerosis. The results suggest that both cell types play important roles in the induction of tolerance through the secretion of specific factors and interaction with CD4 T cells. This mechanistic support provides insights for the development of biomaterial platforms in clinical trials.
Article
Immunology
Antonella Carambia, Cornelia Gottwick, Dorothee Schwinge, Stephanie Stein, Reinaldo Digigow, Muharrem Seleci, Disha Mungalpara, Markus Heine, Fenja A. Schuran, Carlotta Corban, Ansgar W. Lohse, Christoph Schramm, Joerg Heeren, Johannes Herkel
Summary: This study investigated the antigen-specific treatment of CD8 T-cell-driven autoimmune disease by delivering autoantigen peptides to liver sinusoidal endothelial cells using nanoparticles. The results showed that this method effectively reduced liver damage by modulating the number of liver-infiltrating OT-1 T cells, decreasing the expression of the inhibitory receptor PD-1, and suppressing cytotoxic effector function and inflammatory cytokine production.
Article
Cell Biology
Bai Ruan, Juan-Li Duan, Hao Xu, Kai-Shan Tao, Hua Han, Guo-Rui Dou, Lin Wang
Summary: Liver sinusoidal endothelial cells undergo partial endothelial mesenchymal transition during liver fibrosis, leading to increased extracellular matrix production without activating cell mobility. Targeting this transitional process may be valuable for antifibrotic treatment of liver fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Sophia Papaioannou, Jia-Xiang See, Mingeum Jeong, Carolina De La Torre, Volker Ast, Philipp-Sebastian Reiners-Koch, Ankita Sati, Carolin Mogler, Michael Platten, Adelheid Cerwenka, Ana Stojanovic
Summary: Liver sinusoidal endothelial cells (LSECs) respond to LPS and immune-derived signals, producing chemokines CCL2 and CXCL10. NK cells exposed to LSECs in vitro are primed for higher production of IFN-g in response to IL-12 and IL-18. In inflamed livers, NK cells are the major producers of IFN-g. This positive feedback loop of immune cell attraction and activation is regulated by LSECs and is important in liver inflammation.
Review
Gastroenterology & Hepatology
Jordi Gracia-Sancho, Esther Caparros, Anabel Fernandez-Iglesias, Ruben Frances
Summary: Liver sinusoidal endothelial cells (LSECs) play crucial roles in hepatic homeostasis, being involved in regulation of vascular tone, inflammation, and thrombosis, as well as control of the hepatic immune response. Dysregulations of LSECs in the context of liver disease and hepatocellular carcinoma make them potential therapeutic targets.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Review
Cell Biology
Yoshiya Ito, Kanako Hosono, Hideki Amano
Summary: The liver has the ability to regenerate in response to acute liver injury, but liver ischemia-reperfusion injury (IRI) remains a major problem in liver surgery. Non-parenchymal cells in the liver play critical roles in liver repair and regeneration, and recent technological advances have provided insights into their heterogeneity. This review discusses the progress in understanding the biology of liver non-parenchymal cells and the functional role of each cell component in response to liver IRI.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sara Petrillo, Marta Manco, Fiorella Altruda, Sharmila Fagoonee, Emanuela Tolosano
Summary: This article discusses the role of iron in promoting liver fibrosis, focusing on the key role of LSECs in the fibrotic process, and suggests the potential of targeting LSECs as a therapeutic approach in the future.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Review
Immunology
Xiaoqing Chen, Xue Liu, Yichao Jiang, Ningshao Xia, Chao Liu, Wenxin Luo
Summary: Chronic hepatitis B virus (HBV) infection is a major public health challenge, with over 250 million people worldwide infected. Priming of naive HBV-specific CD8 T cells is hindered, and this is closely related to abnormalities in the complex immune microenvironment. In this article, we summarize recent progress in understanding the abnormal priming of HBV-specific CD8 T cells and discuss corresponding immunotherapies to facilitate their functional recovery. We also highlight the importance of balancing viral clearance and pathological liver injury induced by CD8 T-cell activation during drug development.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Pharmacology & Pharmacy
Xue-Kai Wang, Zong-Gen Peng
Summary: NAFLD and its advanced stage NASH pose a global public health threat, with no specific drugs approved for NASH treatment yet promising candidates in development. LSECs have been shown to play a crucial role in liver inflammation of NAFLD, offering potential as a therapeutic target for controlling liver inflammation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Feifei Qiu, Weihui Lu, Shulin Ye, Huazhen Liu, Qiaohuang Zeng, Haiding Huang, Chun-Ling Liang, Yuchao Chen, Fang Zheng, Qunfang Zhang, Chuan-Jian Lu, Zhenhua Dai
Summary: This study demonstrates that berberine prolongs allograft survival by repressing CD8(+) central memory T-cells through regulating the gut microbiota, providing a novel mechanism underlying its therapeutic effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Physiology
Alyssa R. Goldberg, Megan Ferguson, Sarit Pal, Rachel Cohen, David J. Orlicky, Rebecca L. McCullough, Joseph M. Rutkowski, Matthew A. Burchill, Beth A. Jiron Tamburini
Summary: This study investigates the impairment of liver lymphatic function in chronic liver diseases and its underlying mechanisms. The findings suggest that chronic liver diseases, such as NAFLD, ALD, and PSC, lead to impaired lymphatic drainage and increased levels of oxLDL. Furthermore, the study demonstrates that oxLDL decreases the permeability of lymphatic endothelial cells through the regulation of SRC-family kinases, MAPK kinase, and VE-Cadherin. The engagement of VEGFR-3 by its ligands prevents the upregulation of VE-Cadherin and improves lymphatic permeability.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Tingting Su, Yilin Yang, Sanchuan Lai, Jain Jeong, Yirang Jung, Matthew McConnell, Teruo Utsumi, Yasuko Iwakiri
Summary: This study mapped the spatial distribution and transcriptomic changes of liver sinusoidal endothelial cells (LSECs) in normal vs cirrhotic mouse livers, providing insights into the pathogenesis of liver cirrhosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Immunology
Wei Du, Lin Wang
Summary: This article reviews the key role of crosstalk between liver sinusoidal endothelial cells (LSECs) and hepatic microenvironment in the progression of NASH to liver fibrosis, and discusses promising therapeutic strategies targeting LSECs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Yang Wang, Yifan Zhang, Yun Liu, Jun Xu, Yulan Liu
Summary: The study found that LSEC is a crucial barrier in the gut-liver axis, defending the liver against colitis-induced injury. When LSECs are damaged, they can turn into a pro-inflammatory pattern under the stimulation of LPS. LSEC injury and colitis-derived LPS synergistically contribute to the recruitment and activation of hepatic neutrophils. Neutrophils play a pivotal role as a downstream effector in colitis-induced liver injury.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mar Gil, Mikel Azkargorta, Carla Fuster, Maria Martinez-Gomez, Imma Raurell, Aurora Barbera, Juan Manuel Pericas, Diana Hide, Felix Elortza, Joan Genesca, Maria Martell
Summary: This study investigated the molecular profile changes of dysfunctional liver sinusoidal endothelial cells (LSEC) in different pathological scenarios using flow cytometry and proteomics analysis. The expression of proteins in LSEC from disease models showed significant differences compared to control LSEC, with CD32b(-) LSEC showing more pronounced differences. The findings suggest that LSEC in liver disease models have distinct protein expression patterns.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Mariana O. Diniz, Anna Schurich, Senthil K. Chinnakannan, Marion Duriez, Kerstin A. Stegmann, Jessica Davies, Stephanie Kucykowicz, Kornelija Suveizdyte, Oliver E. Amin, Frances Alcock, Tamsin Cargill, Eleanor Barnes, Mala K. Maini
Summary: This study demonstrates that NK cell depletion enhances the immune response to vaccines in a mouse model of chronic HBV infection. It was found that the up-regulation of PD-L1 on liver-resident NK cells and PD-1 on intrahepatic T cells plays a negative regulatory role in the response to therapeutic vaccination. Combining cytokine activation with PD-L1 blockade can convert NK cells into efficient helpers, boosting the CD8(+) T cell response to therapeutic vaccination.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Alexandra Linke, Hakan Cicek, Anne Mueller, Catherine Meyer-Schwesinger, Simon Melderis, Thorsten Wiech, Claudia Wegscheid, Julius Ridder, Oliver M. Steinmetz, Linda Diehl, Gisa Tiegs, Katrin Neumann
Summary: This study found that proximal tubular epithelial cells (PTECs) have the capacity for antigen cross-presentation, which can modulate the immune response in immune-mediated glomerular diseases, such as lupus nephritis.
Article
Cell Biology
Celina Eckfeld, Benjamin Schoeps, Daniel Haeussler, Julian Fraedrich, Felix Bayerl, Jan Philipp Boettcher, Percy Knolle, Simone Heisz, Olga Prokopchuk, Hans Hauner, Enkhtsetseg Munkhbaatar, Ihsan Ekin Demir, Chris D. Hermann, Achim Krueger
Summary: The study reveals that TIMP-1 interacts with APP family members and triggers monocyte activation, leading to proinflammatory cytokine expression. This mechanism is confirmed in clinical cancer samples and suggests that TIMP-1 can be a potential therapeutic target for inflammatory diseases.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Yuhan Yin, Anna Sichler, Josef Ecker, Melanie Laschinger, Gerhard Liebisch, Marcus Hoering, Marijana Basic, Andre Bleich, Xue-Jun Zhang, Ludwig Kuebelsbeck, Johannes Plagge, Emely Scherer, Dirk Wohlleber, Jianye Wang, Yang Wang, Marcella Steffani, Pavel Stupakov, Yasmin Gaertner, Fabian Lohoefer, Carolin Mogler, Helmut Friess, Daniel Hartmann, Bernhard Holzmann, Norbert Hueser, Klaus-Peter Janssen
Summary: Hepatocyte growth and proliferation depend on membrane phospholipid biosynthesis, which is significantly influenced by short-chain fatty acids (SCFAs) generated through bacterial fermentation. Antibiotic treatment and dysbiosis not only affect gut microbiota, but also impair hepatic lipid synthesis and liver regeneration.
JOURNAL OF HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Laura J. Pallett, Leo Swadling, Mariana Diniz, Alexander A. A. Maini, Marius Schwabenland, Adria Dalmau Gasull, Jessica Davies, Stephanie Kucykowicz, Jessica K. K. Skelton, Niclas Thomas, Nathalie M. M. Schmidt, Oliver E. E. Amin, Upkar S. S. Gill, Kerstin A. A. Stegmann, Alice R. R. Burton, Emily Stephenson, Gary Reynolds, Matt Whelan, Jenifer Sanchez, Roel de Maeyer, Clare Thakker, Kornelija Suveizdyte, Imran Uddin, Ana M. M. Ortega-Prieto, Charlotte Grant, Farid Froghi, Giuseppe Fusai, Sabela Lens, Sofia Perez-del-Pulgar, Walid Al-Akkad, Giuseppe Mazza, Mahdad Noursadeghi, Arne Akbar, Patrick T. F. Kennedy, Brian R. R. Davidson, Marco Prinz, Benjamin M. M. Chain, Muzlifah Haniffa, Derek W. W. Gilroy, Marcus Dorner, Bertram Bengsch, Anna Schurich, Mala K. K. Maini
Summary: CD14(+)CD8(+) T cells in the liver exhibit immunomodulatory features and play a role in liver transplantation, infection, and tumors. These cells have high levels of IL-10 and IL-2 production, as well as enhanced antiviral/anti-tumor effector function. Additionally, these cells can enhance the tumor-killing ability of CD8(+) T cells by acquiring the lipopolysaccharide receptor complex from mononuclear phagocytes. Bacterial products and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8(+) T cells.
Review
Gastroenterology & Hepatology
Neda Yahoo, Michael Dudek, Percy Knolle, Mathias Heikenwaelder
Summary: The liver plays a central role in metabolism and immune functions. When overwhelmed by obesity and a sedentary lifestyle, it can lead to the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Genetic and environmental factors, including the gut microbiome, also contribute to the development and progression of NAFLD and liver cancer. CD8+CXCR6+PD1+ T cells are implicated in the transition from NASH to hepatocellular carcinoma (HCC), and their characteristics may affect responses to immune checkpoint inhibitors. This review focuses on the role of T cells in NASH and discusses preventive measures and therapeutic strategies for managing NASH-HCC.
JOURNAL OF HEPATOLOGY
(2023)
Article
Oncology
Sophie Papa, Antonella Adami, Michael Metoudi, Richard Beatson, Molly Sarah George, Daniela Achkova, Evangelia Williams, Sefina Arif, Fiona Reid, Maria Elstad, Nicholas Beckley-Hoelscher, Abdel Douri, Marc Delord, Mike Lyne, Dharshene Shivapatham, Christopher Fisher, Andrew Hope, Sakina Gooljar, Arindam Mitra, Linda Gomm, Cienne Morton, Rhonda Henley-Smith, Selvam Thavaraj, Alice Santambrogio, Cynthia Andoniadou, Sarah Allen, Victoria Gibson, Gary J. R. Cook, Ana C. Parente-Pereira, David M. Davies, Farzin Farzaneh, Anna Schurich, Teresa Guerrero-Urbano, Jean-Pierre Jeannon, James Spicer, John Maher
Summary: This study developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) therapy named T4 immunotherapy for locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC). Patient-derived T-cells were engineered to express a panErbB-specific CAR and an IL-4-responsive chimeric cytokine receptor. Intratumoral delivery was used to mitigate off-tumor toxicity. The study demonstrated the safe and effective intratumoral administration of T4 immunotherapy in advanced HNSCC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Multidisciplinary Sciences
Valter Bergant, Daniel Schnepf, Niklas de Andrade Kraetzig, Philipp Hubel, Christian Urban, Thomas Engleitner, Ronald Dijkman, Bernhard Ryffel, Katja Steiger, Percy A. A. Knolle, Georg Kochs, Roland Rad, Peter Staeheli, Andreas Pichlmair
Summary: Bergant et al. provide evidence that Influenza A viruses cause alternative polyadenylation of host mRNAs, leading to an attenuated phenotype in mice. This may constitute a common immune evasion mechanism employed by a variety of pathogenic viruses.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Jochen M. Wettengel, Katharina Strehle, Catharina von Lucke, Hedwig Roggendorf, Samuel D. Jeske, Catharina Christa, Otto Zelger, Bernhard Haller, Ulrike Protzer, Percy A. Knolle
Summary: This study demonstrates the usefulness of a second-generation rapid antigen test for early detection of infection with the SARS-CoV-2 Omicron variant of concern (VoC) and reveals a higher sensitivity to detect immune escape Omicron VoCs compared to a first-generation rapid antigen test (89.4% vs 83.7%) in the high-risk group of healthcare workers.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Molly S. George, Jenifer Sanchez, Christina Rollings, David Fear, Peter Irving, Linda V. Sinclair, Anna Schurich
Summary: Long-term T cell dysregulation following COVID-19 disease is associated with disease severity and long-covid symptoms. Alterations in cellular origin and protein content of extracellular vesicles (EV) during COVID-19 convalescence are linked to initial disease severity. EV derived from convalescent donors can affect the function and metabolic rewiring of CD4 and CD8 T cells, with immune-suppressive properties observed in mild cases.
Meeting Abstract
Immunology
S. Deschler, L. Ramsauer, J. Pohl, U. Bauer, M. Ringelhan, F. Geisler, R. M. Schmid, J. P. Boettcher, P. A. Knolle, K. Boettcher
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
S. Flommersfeld, M. Pujol, J. P. Boettcher, J. Ersching, M. Flossdorf, P. Meiser, L. O. Pachmayr, J. Leube, I. Hensel, S. Jarosch, Q. Zhang, M. Z. Chaudhry, I. Andrae, M. Schiemann, D. Busch, L. Cicin-Sain, J. C. Sun, G. Gasteiger, G. D. Victora, T. Hoefer, V. Buchholz, S. Grassmann
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
P. Meiser, M. Knolle, A. Hirschberger, G. P. de Almeida, S. Lacher, F. Bayerl, A. -M. Pedde, J. Hoenninger, L. Stark, F. Stoegbauer, M. Anton, M. Wirth, D. Wohlleber, K. Steiger, B. Wollenberg, C. E. Zielinski, R. Braren, D. Rueckert, P. Knolle, G. Kaissis, J. P. Boettcher
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
A. -M. Pedde, H. Kim, S. Donakonda, F. Bayerl, P. Meiser, A. Hirschberger, C. Klement, S. Grassmann, S. Flommersfeld, G. Wiedemann, J. Trapani, M. J. Smyth, V. R. Buchholz, R. Rad, J. C. Sun, J. P. Boettcher
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)