Review
Immunology
Hunter Bennett, Ty D. Troutman, Mashito Sakai, Christopher K. Glass
Summary: Kupffer cells are the resident macrophages of the liver, playing important roles in responses to tissue damage and specialized activities such as iron scavenging. Recent studies have focused on the epigenetic pathways that establish Kupffer cell identity and function.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Laurienne Edgar, Naveed Akbar, Adam T. Braithwaite, Thomas Krausgruber, Hector Gallart-Ayala, Jade Bailey, Alastair L. Corbin, Tariq E. Khoyratty, Joshua T. Chai, Mohammad Alkhalil, Andre F. Rendeiro, Klemen Ziberna, Ritu Arya, Thomas J. Cahill, Christoph Bock, Jurga Laurencikiene, Mark J. Crabtree, Madeleine E. Lemieux, Niels P. Riksen, Mihai G. Netea, Craig E. Wheelock, Keith M. Channon, Mikael Ryden, Irina A. Udalova, Ricardo Carnicer, Robin P. Choudhury
Summary: The study found that hyperglycemia-induced trained immunity may explain the ineffectiveness of targeting elevated glucose in reducing macrovascular risk in diabetes, and suggests new targets for disease prevention and therapy.
Review
Immunology
Yaoyao Xia, Yikun Li, Xiaoyan Wu, Qingzhuo Zhang, Siyuan Chen, Xianyong Ma, Miao Yu
Summary: The review highlights the crucial role of iron in dictating macrophage polarization by orchestrating various aspects such as cellular signaling, cellular metabolism, and epigenetic regulation. Iron modulation affects the development and progression of multiple macrophage-associated diseases, suggesting the potential application of iron supplementation in adjuvant therapy for different inflammatory disorders relative to macrophage polarization balance.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Katherine A. Robinson, Naveed Akbar, Kajus Baidzajevas, Robin P. Choudhury
Summary: Metabolic diseases are associated with inflammation, which negatively affects cardiovascular health. Evidence shows that long-term hyperactivation of innate immune cells and their bone marrow progenitors, known as trained immunity, accelerates atherosclerosis in cardiometabolic diseases. Understanding the mechanisms of trained immunity can lead to the development of novel therapies for reducing cardiovascular risk in metabolic diseases.
Article
Multidisciplinary Sciences
Yohei Kanamori, Miyako Tanaka, Michiko Itoh, Kozue Ochi, Ayaka Ito, Isao Hidaka, Isao Sakaida, Yoshihiro Ogawa, Takayoshi Suganami
Summary: The study reveals that iron accumulation can lead to proinflammatory and profibrotic phenotypic changes in iron-rich Kupffer cells during the development of NASH by activating MiT/TFE transcription factors. Iron chelation effectively attenuates liver fibrosis in a murine NASH model, shedding light on the pathophysiologic role of iron in NASH and a unique macrophage subset rich in iron contributing to CLS formation and liver fibrosis.
Article
Biochemistry & Molecular Biology
Sanjit K. Dhar, Timothy Scott, Chi Wang, Teresa W. M. Fan, Daret K. St Clair
Summary: This study reveals the regulatory role of mitochondrial-generated superoxide radicals in gene expression and establishes a new paradigm that recognizes O2· as an initiator of metabolic reprogramming and epigenetic regulation in response to mitochondrial dysfunction.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Zhengtao Xiao, Jason W. Locasale
Summary: Chromatin and associated epigenetic marks provide important platforms for gene regulation in response to metabolic changes associated with environmental exposures. Studies have shown that fluctuations of key metabolites can influence chromatin modifications, but their effects on chromatin structure are largely unknown.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Review
Immunology
Delphine C. Malherbe, Ilhem Messaoudi
Summary: Drinking alcohol, even in moderation, can have disproportionate effects on the immune system, particularly on myeloid cells. These effects depend on the pattern of alcohol exposure, with acute drinking dampening inflammatory mediators and chronic drinking enhancing their production. Alcohol's impact on myeloid cells is thought to be mediated by oxidative stress and changes in cellular epigenetic landscapes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dalma Cricri, Lara Coppi, Silvia Pedretti, Nico Mitro, Donatella Caruso, Emma De Fabiani, Maurizio Crestani
Summary: Selective inhibition of class I HDACs, particularly HDAC3, improves adipocyte functionality, promotes browning phenotype, and enhances mitochondrial activity in adipocyte precursors. These effects are exerted early in differentiation process and involve modulation of gene expression related to metabolic pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lincon Felipe Lima-Silva, Jennifer Lee, Pedro M. Moraes-Vieira
Summary: Studies have shown that solute carriers play a significant role in regulating macrophage metabolism, affecting mitochondrial activity and intracellular processes, which ultimately impact the functional status of macrophages.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Review
Immunology
Giulia Zago, Pedro H. V. Saavedra, Kayvan R. Keshari, Justin S. A. Perry
Summary: The metabolic state of tissue-resident macrophages directly influences their function, studying metabolic requirements is crucial for understanding their identity, response to inflammatory challenges, and execution of homeostatic functions. Emerging technologies are driving in situ study of tissue-resident macrophage metabolism.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Payel Mondal, Shrikanth S. Gadad, Swagata Adhikari, Enrique Ramos, Sabyasachi Sen, Parash Prasad, Chandrima Das
Summary: TCF19 is a novel glucose and insulin-responsive factor that interacts with tumor suppressor protein p53 to co-regulate a wide array of metabolic genes, directly regulating key genes involved in glycolysis and oxidative phosphorylation. The TCF19/p53 complexes can epigenetically program the expression of metabolic genes depending on glucose conditions and play a fundamental role in mitochondrial energy homeostasis and stress adaptation in cancer cells.
Article
Medicine, Research & Experimental
Jing Zhang, Chuan-Rui Ma, Yun-Qing Hua, Lan Li, Jing-Yu Ni, Yu-Ting Huang, Sophia Esi Duncan, Sheng Li, Shan Gao, Guan-Wei Fan
Summary: Atherosclerosis is characterized by lipid metabolism disorder and inflammation, with macrophages playing a crucial role in disease development. Controlling the polarization of macrophages, reducing inflammation, and promoting autophagy are key strategies for treating atherosclerosis.
Article
Biochemistry & Molecular Biology
Giulia Chinetti, Joseph Carboni, Joseph Murdaca, Claudine Moratal, Brigitte Sibille, Juliette Raffort, Fabien Lareyre, Elixene Jean Baptiste, Reda Hassen-Khodja, Jaap G. Neels
Summary: Patients with type 2 diabetes are less likely to develop abdominal aortic aneurysm (AAA), possibly due to diabetes-induced changes in the metabolism of macrophages. This study found that macrophages treated with serum from diabetic AAA patients showed increased metabolism and a shift towards an anti-inflammatory state, suggesting a potential mechanism for the reduced risk of AAA development in diabetic patients.
Review
Immunology
Maaike Schilperoort, David Ngai, Santosh R. Sukka, Kleopatra Avrampou, Hongxue Shi, Ira Tabas
Summary: The process of macrophages engulfing dying cells, known as efferocytosis, is tightly regulated and involves sensing, binding, engulfment, and digestion of apoptotic cells. Efferocytosis not only prevents tissue necrosis and inflammation caused by secondary necrosis of dying cells, but also promotes pro-resolving signaling in macrophages, which is essential for tissue resolution and repair following injury or inflammation. The cargo released from apoptotic cells after their engulfment and digestion by macrophages, containing amino acids, nucleotides, fatty acids, and cholesterol, plays a crucial role in this pro-resolving reprogramming.
IMMUNOLOGICAL REVIEWS
(2023)
Editorial Material
Gastroenterology & Hepatology
Giuseppe Riccardo Diaferia, Gioacchino Natoli
Article
Cell Biology
Matteo Audano, Silvia Pedretti, Simona Ligorio, Francesco Gualdrini, Sara Polletti, Marta Russo, Serena Ghisletti, Camilla Bean, Maurizio Crestani, Donatella Caruso, Emma De Fabiani, Nico Mitro
Summary: This study identifies zinc finger CCCH-type containing 10 (Zc3h10) as a critical regulator of early adipogenesis, highlighting its role in repressing protein synthesis and promoting F-actin/mitochondria dynamics for proper energy metabolism and lipid accumulation in mature adipocytes.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Marta Milan, Giuseppe R. Diaferia, Gioacchino Natoli
Summary: PDAC is a highly lethal tumor characterized by the heterogeneity of tumor cells, mainly attributed to two main classes of cells - those capable of differentiation towards endodermal, mucin-producing epithelia, and those unable to form glandular structures and instead exhibiting squamous differentiation.
Article
Biochemistry & Molecular Biology
Liv M. I. Austenaa, Viviana Piccolo, Marta Russo, Elena Prosperini, Sara Polletti, Danilo Polizzese, Serena Ghisletti, Iros Barozzi, Giuseppe R. Diaferia, Gioacchino Natoli
Summary: The inefficient splicing of the first exons of enhancer-generated long noncoding RNAs (elncRNAs) and promoter-antisense long noncoding RNAs (pa-lncRNAs) triggers a transcription termination checkpoint that requires specific proteins WDR82 and ZC3H4. This mechanism both enhances protein-coding gene transcription and boosts enhancer activity, while also containing elements that suppress pervasive extragenic transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Bernhard Luscher, Ivan Ahel, Matthias Altmeyer, Alan Ashworth, Peter Bai, Paul Chang, Michael Cohen, Daniela Corda, Francoise Dantzer, Matthew D. Daugherty, Ted M. Dawson, Valina L. Dawson, Sebastian Deindl, Anthony R. Fehr, Karla L. H. Feijs, Dmitri V. Filippov, Jean-Philippe Gagne, Giovanna Grimaldi, Sebastian Guettler, Nicolas C. Hoch, Michael O. Hottiger, Patricia Korn, W. Lee Kraus, Andreas Ladurner, Lari Lehtio, Anthony K. L. Leung, Christopher J. Lord, Aswin Mangerich, Ivan Matic, Jason Matthews, George-Lucian Moldovan, Joel Moss, Gioacchino Natoli, Michael L. Nielsen, Mario Niepel, Friedrich Nolte, John Pascal, Bryce M. Paschal, Krzysztof Pawlowski, Guy G. Poirier, Susan Smith, Gyula Timinszky, Zhao-Qi Wang, Jose Yelamos, Xiaochun Yu, Roko Zaja, Mathias Ziegler
Summary: ADP-ribosylation, a post-translational modification of proteins, nucleic acids, and metabolites, plays diverse roles in cellular processes such as stress responses, signaling, and transcriptional regulation. Recent advances in research have identified a wide range of cellular pathways regulated by ADP-ribosylation, highlighting the importance of understanding this mechanism in cell biology.
Article
Multidisciplinary Sciences
Edoardo Del Poggetto, I-Lin Ho, Chiara Balestrieri, Er-Yen Yen, Shaojun Zhang, Francesca Citron, Rutvi Shah, Denise Corti, Giuseppe R. Diaferia, Chieh-Yuan Li, Sara Loponte, Federica Carbone, Yoku Hayakawa, Giovanni Valenti, Shan Jiang, Luigi Sapio, Hong Jiang, Prasenjit Dey, Sisi Gao, Angela K. Deem, Stefan Rose-John, Wantong Yao, Haoqiang Ying, Andrew D. Rhim, Giannicola Genovese, Timothy P. Heffernan, Anirban Maitra, Timothy C. Wang, Linghua Wang, Giulio F. Draetta, Alessandro Carugo, Gioacchino Natoli, Andrea Viale
Summary: Inflammation plays a key role in promoting pancreatic ductal adenocarcinoma (PDAC), especially in the presence of KRAS mutations. Researchers have found that a transient inflammatory event can prime pancreatic epithelial cells for subsequent transformation by oncogenic KRAS, even long after the inflammation has resolved. This adaptation allows for the reactivation of acinar-to-ductal metaplasia (ADM) in response to recurring inflammatory events, potentially offering a protective mechanism against tissue damage.
Article
Multidisciplinary Sciences
Chiara Ronchini, Sara Gandini, Sebastiano Pasqualato, Luca Mazzarella, Federica Facciotti, Marina Mapelli, Gianmaria Frige', Rita Passerini, Luca Pase, Silvio Capizzi, Fabrizio Mastrilli, Roberto Orecchia, Gioacchino Natoli, Pier Giuseppe Pelicci
Summary: In this study, we found that the probability of infection post-vaccination is significantly lower compared to natural infection, and the duration of infection is shorter. These findings are negatively correlated with circulating antibody levels.
Article
Biochemistry & Molecular Biology
Michele Chirichella, Niccolo Bianchi, Emina Dzafo, Elena Foli, Francesco Gualdrini, Amy Kenyon, Gioacchino Natoli, Silvia Monticelli
Summary: miR-150 is highly expressed in primary human memory T helper lymphocytes, and its downregulation upon activation is associated with the reduced expression of RFX family of transcription factors. The RNA-binding protein PDAP1 is identified as one main target of miR-150 in human T lymphocytes, and its deletion significantly contributes to the regulation of T-cell proliferation.
Article
Cell Biology
Francesco Gualdrini, Sara Polletti, Marta Simonatto, Elena Prosperini, Francesco Pileri, Gioacchino Natoli
Summary: This study found that the loss of H3K9me3 caused by SETDB1 depletion led to increased recruitment of CTCF to SINE B2 repeats, which influenced chromatin organization and gene regulation.
GENES & DEVELOPMENT
(2022)
Editorial Material
Immunology
Francesco Pileri, Gioacchino Natoli
Summary: Mutations in DNMT3A and TET2, regulators of DNA methylation, are linked to clonal hematopoiesis and increased risk of cardiovascular disorders. Cobo et al. discovered that the loss of mitochondrial integrity, dispersion of mitochondrial DNA, and activation of ISGs in macrophages contribute to these associations.
TRENDS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Judith Barbara Zaugg, Pelin Sahlen, Robin Andersson, Meritxell Alberich-Jorda, Wouter de Laat, Bart Deplancke, Jorge Ferrer, Susanne Mandrup, Gioacchino Natoli, Dariusz Plewczynski, Alvaro Rada-Iglesias, Salvatore Spicuglia
Summary: Enhancers are crucial for the spatiotemporal control of gene expression and are cell-type-specific. They are suggested to contribute to phenotypic variation, evolution, and disease. Dysfunction of enhancers, caused by genetic, structural, or epigenetic mechanisms, has been linked to a broad range of human diseases, known as enhanceropathies. Understanding how enhancer dysfunction affects gene expression remains a challenge.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)