Article
Immunology
Juan E. Tichauer, Gabriel Arellano, Eric Acuna, Luis F. Gonzalez, Nirmal R. Kannaiyan, Paola Murgas, Concepcion Panadero-Medianero, Jorge Ibanez-Vega, Paula I. Burgos, Eileah Loda, Stephen D. Miller, Moritz J. Rossner, Peter J. Gebicke-Haerter, Rodrigo Naves
Summary: Compelling evidence indicates that interferon (IFN)-gamma has both pathogenic and beneficial effects in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which IFN-gamma promotes neuroprotection and its effects on central nervous system (CNS)-resident cells have remained unknown. This study investigated the impact of IFN-gamma on CNS infiltrating myeloid cells and microglia in EAE and revealed its therapeutic activity through the induction of homeostatic microglial subsets and regulation of gene expression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
E. A. Innis, C. Levinger, M. A. Szaniawski, E. S. C. P. Williams, J. Alcami, A. Bosque, J. T. Schiffer, M. Coiras, A. M. Spivak, V Planelles
Summary: This study investigated FDA-approved oncology drugs and found that dasatinib, ponatinib, and trametinib can significantly reduce proliferation of memory CD4 T cells in HIV-infected individuals. Dasatinib, in particular, blocks both homeostatic and antigen-driven proliferation and aids in reducing the reservoir size. By inhibiting STAT5 phosphorylation, dasatinib hinders IL-7 induced proliferation and prevents spontaneous rebound in cells from people living with HIV-1.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Immunology
Hao Wu, Chunqing Guo, Zheng Liu, Jinyang Cai, Chong Wang, Huanfa Yi, Arun Sanyal, Puneet Puri, Huiping Zhou, Xiang-Yang Wang
Summary: Drug-associated hepatotoxicity, particularly acetaminophen-induced liver injury (AILI), is a major cause of acute liver failure. This study reveals that serum levels of the pro-inflammatory cytokine interferon (IFN)- γ correlate with disease severity in patients with drug hepatotoxicity. The researchers found that hepatic neutrophils are the primary source of IFN- γ production in response to APAP-injured hepatocytes, and inhibition of IFN- γ effectively reduces hepatotoxicity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tomohiro Watanabe, Kosuke Minaga, Hajime Honjo, Masatoshi Kudo
Summary: The liver showed hypo-responsiveness to antigens and high doses of orally-administered ovalbumin (OVA) generated unique CD4+ T cells and tolerogenic dendritic cells that can suppress Th1 responses. OVA administration at high doses inhibited hepatitis development in mice with OVA-specific CD4+ T cells, and this was associated with downregulation of Th1 responses. The results suggest that high-dose oral antigen administration can suppress Th1-mediated hepatitis in an antigen-non-specific manner.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Weronika Sowinska, Mateusz Wawro, Debolina D. Biswas, Jakub Kochan, Katarzyna Pustelny, Aleksandra Solecka, Angela S. Gupta, Karli Mockenhaupt, Jaroslaw Polak, Borys Kwinta, Tomasz Kordula, Aneta Kasza
Summary: The precise functions of Regnase-2 (Reg-2/ZC3H12B/MCPIP2) and its regulatory mechanisms remain unclear. This study shows that Reg-2 actively controls neuroinflammation in nontransformed cells, particularly primary astrocytes. It downregulates the mRNA levels of proinflammatory cytokines IL-1 beta and IL-6, as well as regulates the expression of Regnase-1 (Reg-1/ZC3H12A/MCPIP1). The expression levels of Reg-2 and Reg-1 are inversely related and their imbalance is associated with glioblastoma progression and patient prognosis.
Editorial Material
Biochemistry & Molecular Biology
Min Woo Kim, Jonathan Kipnis
Summary: This study demonstrates that opioid use affects the communication between the central nervous system and the peripheral immune system, leading to changes in T cell and cytokine modulation of brain function, and is associated with withdrawal-induced behavioral dysfunction.
Article
Multidisciplinary Sciences
Xiaolei Wang, Terrence Tsz-Tai Yuen, Ying Dou, Jingchu Hu, Renhao Li, Zheng Zeng, Xuansheng Lin, Huarui Gong, Celia Hoi-Ching Chan, Chaemin Yoon, Huiping Shuai, Deborah Tip-Yin Ho, Ivan Fan-Ngai Hung, Bao-Zhong Zhang, Hin Chu, Jian-Dong Huang
Summary: Researchers demonstrate the importance of cellular immunity in protecting against SARS-CoV-2 by showing that mice lacking B cells can still develop a robust immune response through vaccination or viral challenge. This study has important implications for understanding the impact of SARS-CoV-2 variants on the immune system.
NATURE COMMUNICATIONS
(2023)
Article
Polymer Science
Joel P. Joseph, Sriram Bharath Gugulothu, Dipankar Nandi, Kaushik Chatterjee
Summary: T cells play a critical role in the immune response and their activation and response can be influenced by the 3D bioprinted matrix and its stiffness. The study reveals differences between 2D and 3D cultures and the impact of matrix stiffness on T cell activation and cytokine release.
Article
Multidisciplinary Sciences
Zhaowei Chen, Binjie Li, Ren-Zhi Zhan, Lingjun Rao, Nenad Bursac
Summary: In this study, the effects of exercise-mimetic electrical stimulation (E-stim) on interferon-gamma (IFN-γ)-induced muscle weakness were investigated using an in vitro tissue-engineered model of human skeletal muscle (myobundle). The results showed that E-stim attenuated IFN-γ-induced muscle wasting and weakness, in part by down-regulating the JAK/STAT signaling pathway amplified by IFN-γ. These findings reveal a previously unknown mechanism of the cell-autonomous anti-inflammatory effects of muscle exercise.
Article
Immunology
Emily Feng, Jonathan K. Monteiro, Ana L. Portillo, Elizabeth Balint, Ali A. Ashkar
Summary: Regulation of immune responses during viral infection is critical to prevent immunopathology. NK cells not only promote viral clearance but also limit immune-mediated tissue damage. Our study reveals the immunoregulatory function of NK cells in suppressing IL-6-mediated pathogenic responses in macrophages, highlighting the potential of NK cell therapy for severe viral infections.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Shilpi Giri, Girdhari Lal
Summary: Gamma-delta (γδ) T cells are a heterogeneous population of immune cells that make up <5% of total T cells in mice lymphoid tissue and human peripheral blood. They play important roles in immune functions, tissue repair, and maintaining homeostasis, especially in epithelial and mucosal barriers. These tissue-resident γδ T cells possess properties of both innate and adaptive immune cells, enabling them to participate in various functions during homeostasis and diseases, including transplant rejection and survival. Their functions can be modulated through interactions with other immune cells.
MOLECULAR IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoling Xie, Wuju Zhang, Xuan Zhou, Binyan Xu, Hao Wang, Yingqi Qiu, Yuxing Hu, Bin Guo, Zhixin Ye, Le Hu, Honghao Zhang, Yuhua Li, Xiaochun Bai
Summary: Low serum IFN-gamma levels are associated with a higher percentage of LSCs and greater relapse incidence in AML patients. High doses of IFN-gamma have an anti-AML effect, while low doses accelerate AML development and support LSC self-renewal. Targeting IFNGR1 in AML cells induces differentiation and delays leukemogenesis.
Article
Cell Biology
Paolo Strati, Xubin Li, Qing Deng, Mario L. Marques-Piubelli, Jared Henderson, Grace Watson, Laurel Deaton, Taylor Cain, Haopeng Yang, Vida Ravanmehr, Luis E. Fayad, Swaminathan P. Iyer, Loretta J. Nastoupil, Frederick B. Hagemeister, Edwin R. Parra, Neeraj Saini, Koichi Takahashi, Nathan H. Fowler, Jason R. Westin, Raphael E. Steiner, Ranjit Nair, Christopher R. Flowers, Linghua Wang, Sairah Ahmed, Gheath Al-Atrash, Francisco Vega, Sattva S. Neelapu, Michael R. Green
Summary: Autologous anti-CD19 CAR T therapy shows high effectiveness in rrLBCL, but its toxicities result in delayed recovery. The pathophysiology of prolonged cytopenia after CAR T infusion is poorly understood. Single-cell RNA sequencing reveals that clonally expanded CX3CR1(hi) cytotoxic T cells with high IFN-g and cytokine signaling are associated with prolonged cytopenia, suggesting a potential mechanism-based approach for its treatment.
CELL REPORTS MEDICINE
(2023)
Article
Multidisciplinary Sciences
Carolyn A. Cohen, Athena P. Y. Li, Asmaa Hachim, David S. C. Hui, Mike Y. W. Kwan, Owen T. Y. Tsang, Susan S. Chiu, Wai Hung Chan, Yat Sun Yau, Niloufar Kavian, Fionn N. L. Ma, Eric H. Y. Lau, Samuel M. S. Cheng, Leo L. M. Poon, J. S. Malik Peiris, Sophie A. Valkenburg
Summary: This study shows that infected children have lower CD4(+) and CD8(+) T cell responses to SARS-CoV-2 proteins compared to infected adults. Children also have reduced CD4(+) T cell effector memory but comparable T cell polyfunctionality.
NATURE COMMUNICATIONS
(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.
Article
Medicine, General & Internal
Philippe Decruyenaere, Beatrice Van de Maele, Eva Hulstaert, Hans Van Vlierberghe, Johan Decruyenaere, Hilde Lapeere
Summary: This article presents a case of gastro-allergic anisakiasis in a 58-year-old woman who developed acute IgE-mediated hypersensitivity reaction and gastrointestinal symptoms after consuming raw fish. It highlights the importance of considering Anisakis allergy as a potential cause for patients with urticarial rash, anaphylaxis, and abdominal symptoms, particularly after seafood consumption. The article also emphasizes the rare but significant complication of eosinophilic esophagitis in Anisakis infection.
ACTA CLINICA BELGICA
(2022)
Article
Cell Biology
Lindsey Devisscher, Sanne Van Campenhout, Sander Lefere, Sarah Raevens, Laurentijn Tilleman, Filip Van Nieuwerburgh, Hannelore P. Van Eeckhoutte, Anne Hoorens, Michael A. Lynes, Anja Geerts, Debby Laukens, Hans Van Vlierberghe
Summary: APAP intoxication leads to liver injury, with MT playing a key role in the process. Anti-MT antibody therapy can alleviate liver damage.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Martin Guilliams, Johnny Bonnardel, Birthe Haest, Bart Vanderborght, Camille Wagner, Anneleen Remmerie, Anna Bujko, Liesbet Martens, Tinne Thone, Robin Browaeys, Federico F. De Ponti, Bavo Vanneste, Christian Zwicker, Freya R. Svedberg, Tineke Vanhalewyn, Amanda Goncalves, Saskia Lippens, Bert Devriendt, Eric Cox, Giuliano Ferrero, Valerie Wittamer, Andy Willaert, Suzanne J. F. Kaptein, Johan Neyts, Kai Dallmeier, Peter Geldhof, Stijn Casaert, Bart Deplancke, Peter ten Dijke, Anne Hoorens, Aude Vanlander, Frederik Berrevoet, Yves Van Nieuwenhove, Yvan Saeys, Wouter Saelens, Hans Van Vlierberghe, Lindsey Devisscher, Charlotte L. Scott
Summary: This study presents a spatial proteogenomic atlas of the liver, combining multiple omics datasets, and reveals the cellular niches and transcriptomic identities of Kupffer cells and lipid-associated macrophages. It also demonstrates the inducibility of lipid-associated macrophages by local lipid exposure and the crucial role of ALK1-BMP9/10 axis in Kupffer cell development.
Article
Gastroenterology & Hepatology
Sander Lefere, Ellen Dupont, Ann De Guchtenaere, Stephanie Van Biervliet, Saskia Vande Velde, Xavier Verhelst, Lindsey Devisscher, Hans Van Vlierberghe, Anja Geerts, Ruth De Bruyne
Summary: NAFLD and associated fibrosis are highly prevalent in children and adolescents with severe obesity. An intensive multidisciplinary lifestyle management program not only improves liver steatosis, but also fibrosis.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Andrea Schlegel, Marjolein van Reeven, Kristopher Croome, Alessandro Parente, Annalisa Dolcet, Jeannette Widmer, Nicolas Meurisse, Riccardo De Carlis, Amelia Hessheimer, Ina Jochmans, Matteo Mueller, Otto B. van Leeuwen, Amit Nair, Koji Tomiyama, Ahmed Sherif, Mohamed Elsharif, Philipp Kron, Danny van der Helm, Daniel Borja-Cacho, Humberto Bohorquez, Desislava Germanova, Daniele Dondossola, Tiziana Olivieri, Stefania Camagni, Andre Gorgen, Damiano Patrono, Matteo Cescon, Sarah Croome, Rebecca Panconesi, Mauricio Flores Carvalho, Matteo Ravaioli, Juan Carlos Caicedo, George Loss, Valerio Lucidi, Gonzalo Sapisochin, Renato Romagnoli, Wayel Jassem, Michele Colledan, Luciano De Carlis, Giorgio Rossi, Fabrizio Di Benedetto, Charles M. Miller, Bart van Hoek, Magdy Attia, Peter Lodge, Roberto Hernandez-Alejandro, Olivier Detry, Cristiano Quintini, Gabriel C. Oniscu, Constantino Fondevila, Massimo Malago, Jacques Pirenne, Jan N. M. IJzermans, Robert J. Porte, Philipp Dutkowski, C. Burcin Taner, Nigel Heaton, Pierre-Alain Clavien, Wojciech G. Polak, Paolo Muiesan
Summary: The study established the best possible outcomes and reference values for liver transplantation using grafts donated after circulatory death (DCD) through benchmarking. The benchmark cases showed excellent 1-year retransplant and mortality rates, but had high rates of major complications. The use of organ perfusion technology reduced complications and improved outcomes in high-risk patients.
JOURNAL OF HEPATOLOGY
(2022)
Article
Medicine, General & Internal
Nicky Somers, Elisabeth Vandekerckhove, Anja Geerts, Helena Degroote, Sander Lefere, Lindsey Devisscher, Leander Meuris, Nico Callewaert, Hans Van Vlierberghe, Xavier Verhelst
Summary: This study assessed the inflammation-related fibrosis regression during and after treatment of HCV with DAAs using serum glycomics. The results suggest that GlycoFibroTest is a serum biomarker for viral response in HCV patients, and the rapid decrease of this glycomics-based biomarker may reflect the improvement of liver inflammation.
ACTA CLINICA BELGICA
(2023)
Article
Biochemistry & Molecular Biology
Nathan Carpentier, Louis Van der Meeren, Andre G. Skirtach, Lindsey Devisscher, Hans Van Vlierberghe, Peter Dubruel, Sandra Van Vlierberghe
Summary: This study developed Dexox-Gel and DexNB-GelSH hydrogels and investigated their processability and in vitro biocompatibility. The results showed that DexNB-GelSH exhibited physicochemical properties similar to natural liver tissue and had comparable performance to GelMA in biological evaluation, indicating its promising potential in the field of liver tissue engineering.
Article
Gastroenterology & Hepatology
Maaike Biewenga, Xavier Verhelst, Martine Baven-Pronk, Hein Putter, Aad van den Berg, Isabelle Colle, Jeoffrey Schouten, Filip Sermon, Christophe Van Steenkiste, Hans van Vlierberghe, Adriaan van der Meer, Bart van Hoek
Summary: In patients with autoimmune hepatitis, low levels of aminotransferases during treatment are associated with better long-term survival, while immunoglobulin G is not associated with survival in the first 12 months of treatment.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Review
Oncology
Helena Degroote, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe
Summary: Liver transplantation is the preferred treatment for early-stage hepatocellular carcinoma. However, there is a risk of recurrence in the transplanted liver, and predicting this risk and related prognosis for individual patients is challenging. Various scoring systems have been proposed, but there is no consensus on the optimal model or its implications in clinical practice.
Article
Multidisciplinary Sciences
Wouter Claeys, Lien Van Hoecke, Anja Geerts, Hans Van Vlierberghe, Sander Lefere, Griet Van Imschoot, Elien Van Wonterghem, Bart Ghesquiere, Roosmarijn E. Vandenbroucke, Christophe Van Steenkiste
Summary: This study provides a comprehensive evaluation of a mouse model of hepatic encephalopathy and highlights the importance of neuroinflammation in the central effects of chronic liver disease.
SCIENTIFIC REPORTS
(2022)
Article
Gastroenterology & Hepatology
Louise Magherman, Robbe Van Parys, Nele S. Pauwels, Xavier Verhelst, Lindsey Devisscher, Hans Van Vlierberghe, Anja Geerts, Sander Lefere
Summary: This study examined the impact of light-to-moderate alcohol consumption on progressive NAFLD and mortality. It found that moderate alcohol intake increased the risk of advanced fibrosis, liver cirrhosis, and hepatocellular carcinoma. However, light alcohol consumption appeared to protect against all-cause mortality and lower the risk of steatohepatitis. Further research is needed to provide valid recommendations for alcohol consumption in NAFLD patients.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pathology
Kevin De Muynck, Bart Vanderborght, Federico F. De Ponti, Eva Gijbels, Sophie Van Welden, Martin Guilliams, Charlotte L. Scott, Alain Beschin, Mathieu Vinken, Sander Lefere, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe, Lindsey Devisscher
Summary: Primary sclerosing cholangitis (PSC) is a chronic immune-mediated liver disease characterized by bile duct strictures and fibrosis. The role of hepatic macrophages (MFs) in PSC pathogenesis is unclear. This study found that resident Kupffer cells (ResKCs) were depleted during chronic liver injury, while infiltrating monocyte-derived cells (MoKCs) were enriched during the acute phase of PSC. Depletion of KCs did not affect disease outcomes. These findings provide new insights into the heterogeneity of MFs in PSC and suggest that resident and activated KCs do not play a major role in disease progression.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Infectious Diseases
Roos van den Noortgate, Maja Kiselinova, Celine Sys, Geraldine Accou, Guy Laureys, Hans Van Vlierberghe, Frederik Berrevoet, Elke O. Kreps
Summary: We present a rare case of bilateral ocular toxoplasmosis and concurrent subacute toxoplasma encephalitis in a 70-year-old patient on anti-CD40 treatment following his liver transplant. The patient has been successfully treated with sulfamethoxazole-trimethoprim 800/160 mg, which led to complete resolution of the symptoms. Iatrogenic blockade of the CD40 pathway may increase susceptibility for CNS reactivation of T. gondii.
CASE REPORTS IN INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Eva Gijbels, Kevin De Muynck, Bart Vanderborght, Tim Meese, Filip Van Nieuwerburgh, Aude Vanlander, Frederik Berrevoet, Bart Hendrikx, Anne Hoorens, Hans Van Vlierberghe, Mathieu Vinken, Lindsey Devisscher
Article
Gastroenterology & Hepatology
Charlotte Costentin, Federico Pinero, Helena Degroote, Andrea Notarpaolo, Ilka F. Boin, Karim Boudjema, Cinzia Baccaro, Luis G. Podesta, Philippe Bachellier, Giuseppe Maria Ettorre, Jaime Poniachik, Fabrice Muscari, Fabrizio Dibenedetto, Sergio Hoyos Duque, Ephrem Salame, Umberto Cillo, Sebastian Marciano, Claire Vanlemmens, Stefano Fagiuoli, Patrizia Burra, Hans Van Vlierberghe, Daniel Cherqui, Quirino Lai, Marcelo Silva, Fernando Rubinstein, Christophe Duvoux
Summary: Reassessing the risk of recurrence after liver transplantation (LT) is critical for optimizing the management of patients with hepatocellular carcinoma (HCC). In this study, a new model called R3-AFP was designed and validated based on variables associated with recurrence post-LT, providing a robust framework for designing post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC patients. The R3-AFP model outperformed the original R3 model, which was solely based on explant features.
