Article
Genetics & Heredity
Giulia Carini, Jessica Mingardi, Francesco Bolzetta, Alberto Cester, Andrea Bolner, Giampietro Nordera, Luca La Via, Alessandro Ieraci, Isabella Russo, Stefania Maggi, Stefano Calza, Maurizio Popoli, Nicola Veronese, Laura Musazzi, Alessandro Barbon
Summary: The study aimed to identify potential frailty biomarkers and candidate mechanisms, finding two miRNAs that significantly differentiate frail patients from robust subjects. The potential molecular mechanisms and cellular pathways regulated by these miRNAs in frailty were further explored using bioinformatics tools.
Review
Gastroenterology & Hepatology
Duan-Rui Qiao, Guan-Yue Shan, Shuai Wang, Jun-Ya Cheng, Wei-Qun Yan, Hai-Jun Li
Summary: This article outlines the impact of hepatocellular carcinoma (HCC) on the mononuclear phagocyte system (MPS). It elaborates on how HCC reshapes MPS cell phenotype and the production of associated cytokines, as well as characterizes the function and impairment of the MPS in HCC.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Immunology
Harry Robertson, Jennifer Li, Hani Jieun Kim, Jake W. Rhodes, Andrew N. Harman, Ellis Patrick, Natasha M. Rogers
Summary: The research team successfully identified an independent set of differentially expressed genes characterizing human tolerogenic DC (tolDC) by analyzing transcriptomic data. By validating this transcriptomic signature and exploring gene differences according to the method of tolDC generation, the study potentially offers insights into transcriptional regulators of tolerance and standardized identification of tolDC in clinical trials.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Xu Shi, Hu Zhao, Yafei Kang, Xinyi Dong, Caiqian Yu, Qinying Xie, Yonggang Duan, Aihua Liao, Donghui Huang
Summary: This article outlines the role of mononuclear macrophages in the immune balance of the testes and epididymis and aims to understand the inner immune regulation mechanism. The review concludes that MPS exhibits a precise balance in the male reproductive system, maintaining immune tolerance and defense against pathogens.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Martyna Cieslik, Krzysztof Bryniarski, Katarzyna Nazimek
Summary: Currently, extracellular vesicles (EVs) are considered promising for cell-free therapies, but their effectiveness is limited by rapid clearance by the mononuclear phagocyte system (MPS). Strategies to avoid EV elimination are necessary for their clinical application. On the other hand, dysfunctional MPS is associated with immune-related pathologies, which could potentially be reversed by EVs through modulating macrophage phenotype or regulating antigen presentation by dendritic cells. Targeting EVs to MPS macrophages for replication and repackaging of their molecules into new vesicle subtype can enable specific targeting to desired cells. Further research on MPS-EV interactions is needed for the therapeutic use of EVs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
William J. Olson, Emmanuel Derudder
Summary: Immunity in a naive organism is tightly controlled, with adequate proportions of immune cell subsets and dynamic positioning for efficient responses. The miR-142 miRNAs from the miR-142 locus play important roles in shaping vertebrate immunity, particularly in the generation, migration, and survival of hematopoietic cells.
IMMUNOLOGY LETTERS
(2023)
Article
Oncology
Massimo Re, Marco Tomasetti, Federica Monaco, Monica Amati, Corrado Rubini, Maria P. Foschini, Giacomo Sollini, Federico Maria Gioacchini, Ernesto Pasquini, Lory Santarelli
Summary: The study identified a miRNA cluster in sinonasal inverted papilloma (SNIP) that may help evaluate the risk of transformation into sinonasal squamous cell carcinoma (SNSCC). The miR-449 cluster was found to be upregulated in SNIP and significantly downregulated in SNSCC, suggesting its involvement in the molecular pathogenesis of SNIP and its malignant transformation.
Article
Endocrinology & Metabolism
Vicente Herrero-Aguayo, Juan M. Jimenez-Vacas, Prudencio Saez-Martinez, Enrique Gomez-Gomez, Juan L. Lopez-Canovas, Lourdes Garrido-Sanchez, Aura D. Herrera-Martinez, Laura Garcia-Bermejo, Manuel Macias-Gonzalez, Jose Lopez-Miranda, Justo P. Castano, Manuel D. Gahete, Raul M. Luque
Summary: The study revealed that miR-4454 levels were higher in plasma of obese individuals and associated with insulin resistance, highlighting its potential as a target for obesity-related interventions. miR-4454 was found to be highly expressed in prostate and liver tissues, regulated by insulin, and may impair cellular response to insulin, particularly in prostate gland, through modulation of the splicing process.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Immunology
Chloe M. Doyle, Erica E. Vine, Kirstie M. Bertram, Heeva Baharlou, Jake W. Rhodes, Suat Dervish, Martijn P. Gosselink, Angelina Di Re, Geoffrey P. Collins, Faizur Reza, James W. T. Toh, Nimalan Pathma-Nathan, Golo Ahlenstiel, Grahame Ctercteko, Anthony L. Cunningham, Andrew N. Harman, Scott N. Byrne
Summary: This study discusses the importance of isolating and analyzing mononuclear phagocytes from fresh human tissue to understand their role in the immune system and diseases. The challenges of freeing these cells from tissue, including susceptibility to enzymatic cleavage and cell death, as well as immunological activation/maturation during the extraction process, are highlighted. The methods for anatomical separation of mucosa and submucosa, enzyme digestion optimization, and antibody clone selection for flow cytometry analysis are described, along with the ability to sort functional, immature intestinal dendritic cells for further functional assays.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Tina Ruzic, Vanda Juranic Lisnic, Hana Mahmutefendic Lucin, Tihana Lenac Rovis, Jelena Zeleznjak, Maja Cokaric Brdovcak, Ana Vrbanovic, Deni Oreb, Daria Kvestak, Kristina Gotovac Jercic, Fran Borovecki, Pero Lucin, Barbara Adler, Stipan Jonjic, Berislav Lisnic
Summary: This study investigates the properties and function of the M116 gene region in MCMV, revealing that it encodes a novel protein, M116.1p, which plays a crucial role in the infection of mononuclear phagocytes and viral spread. The study also highlights the similarities between M116.1p and other positional homologs in HCMV and RCMV, further expanding our understanding of the virally encoded glycoproteins involved in viral infectivity and tropism.
JOURNAL OF VIROLOGY
(2022)
Article
Anatomy & Morphology
G. Lazzarini, F. Abramo, F. Albanese, A. Pirone, V. Miragliotta
Summary: The mononuclear phagocyte system (MPS) consists of dispersed mononuclear monocytes and macrophages, which are distinguished from polymorphonuclear cells. The reliable identification of MPS cells is crucial for establishing specific therapies. This study aimed to establish a protocol to identify the proportion of macrophages within the mononuclear phagocyte system using immunofluorescence protocols.
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER
(2023)
Article
Endocrinology & Metabolism
Nicola Murgia, Yuan Ma, Syeda Sadia Najam, Yu Liu, Joanna Przybys, Chenkai Guo, Witold Konopka, Ilya A. Vinnikov
Summary: In this study, the researchers demonstrate the protective effect of miR-15a-5p against obesity using an in vivo reductionist approach. They also identify Bace1 as a direct target of miR-15a-5p, a gene previously linked to energy metabolism imbalance. This research provides important insights into the non-coding RNA-mediated regulation of energy homeostasis and its potential contribution to the development of novel therapeutic approaches for metabolic diseases.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Immunology
Qian Zhu, Jian He, Yangyang Cao, Xiaoli Liu, Wanyun Nie, Fei Han, Peng Shi, Xiao Z. Shen
Summary: This study successfully delineated the different subsets of monocytes, macrophages, and dendritic cells in the kidney using flow cytometry and various techniques. It found that the renal macrophage pool is continuously replenished by bone marrow-derived monocytes and there are also embryonic-derived resident macrophages. The findings provide valuable insights into the biology of renal mononuclear phagocytes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Zhen-Xiao Teng, Xuan-Chen Zhou, Run-Tong Xu, Fang-Yuan Zhu, Xin Bing, Na Guo, Lei Shi, Wen-Wen Qi, Cheng-Cheng Liu, Ming Xia
Summary: This study found that Tfhs-derived exosomes induce DC maturation by regulating the miR-142-5p/CDK5/STAT3 signaling pathway, thereby promoting the occurrence of allergic rhinitis.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Mingyuan Du, Cristina Espinosa-Diez, Mingjun Liu, Ibrahim Adeola Ahmed, Sidney Mahan, Jianxin Wei, Adam L. Handen, Stephen Y. Chan, Delphine Gomez
Summary: miRNAs play versatile roles in regulating smooth muscle cell fate and behavior during vascular development and disease. The miR-200 cluster is found to be downregulated during SMC dedifferentiation and acts as a mechanism to maintain SMC quiescence and inhibit proliferation, migration, and neointima formation by targeting Quaking.
Correction
Cell & Tissue Engineering
Berengere de Laval, Julien Maurizio, Prashanth K. Kandalla, Gabriel Brisou, Louise Simonnet, Caroline Huber, Gregory Gimenez, Orit Matcovitch-Natan, Susanne Reinhardt, Eyal David, Alexander Mildner, Achim Leutz, Bertrand Nadel, Christophe Bordi, Ido Amit, Sandrine Sarrazin, Michael H. Sieweke
Article
Immunology
Kaveri Banerjee, Avinoam Ratzabi, Itai M. Caspit, Or Ganon, Pablo Blinder, Steffen Jung, Reuven Stein
Summary: Gliomas, the most common primary brain tumors, are influenced by the tumor microenvironment comprised of tumor-associated microglia (TA-MG) and monocyte-derived macrophages (MDM). This study reveals the distinct spatial and temporal differences between TA-MG and MDM during glioma progression. TA-MG are found both inside and outside the tumor but are eliminated as the tumor progresses, while MDM are only present inside the tumor. Additionally, the study shows that TA-MG and MDM exhibit different enrichment in the perivascular area. These findings highlight the unique roles of TA-MG and MDM in glioma progression.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Hematology
Avigail Rein, Ifat Geron, Eitan Kugler, Hila Fishman, Eyal Gottlieb, Ifat Abramovich, Amir Giladi, Ido Amit, Roger Mulet-Lazaro, Ruud Delwel, Stefan Groeschel, Smadar Levin-Zaidman, Nili Dezorella, Vered Holdengreber, Tata Nageswara Rao, Joanne Yacobovich, Orna Steinberg-Shemer, Qiu-Hua Huang, Yun Tan, Sai-Juan Chen, Shai Izraeli, Yehudit Birger
Summary: Mono-allelic germline disruptions of the GATA2 transcription factor can lead to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This study shows the role of GATA2 mutations in the development of AML and identifies mitochondrial abnormalities as a potential therapeutic target for preventing leukemic transformation.
Article
Immunology
Saskia Rauber, Christina B. Schroeter, Christine Strippel, Christopher Nelke, Tillmann Ruland, Andre Dik, Kristin S. Golombeck, Liesa Regner-Nelke, Manuela Paunovic, Daniela Esser, Christian Muench, Felix Rosenow, Martijn van Duijn, Antonia Henes, Tobias Ruck, Ido Amit, Frank Leypoldt, Maarten J. Titulaer, Heinz Wiendl, Sven G. Meuth, Gerd Meyer zu Horste, Nico Melzer
Summary: Autoimmune encephalitis (AE) is a group of non-infectious inflammatory conditions of the central nervous system caused by an imbalanced immune response. Analysis of cerebrospinal fluid (CSF) protein profiles in AE patients with different autoantibodies revealed dysregulation in the complement system, imbalance between pro-inflammatory and anti-inflammatory proteins, dysregulation of proteins involved in synaptic transmission and neurodegeneration, as well as elevated levels of proteases and reduced protease inhibitors. Furthermore, distinct protein profiles were found in different AE subtypes, which may aid in identifying disease-specific biomarkers.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Neurosciences
Sebastiaan De Schepper, Judy Z. Z. Ge, Gerard Crowley, Lais S. S. Ferreira, Dylan Garceau, Christina E. E. Toomey, Dimitra Sokolova, Javier Rueda-Carrasco, Sun-Hye Shin, Jung-Seok Kim, Thomas Childs, Tammaryn Lashley, Jemima J. J. Burden, Michael Sasner, Carlo Sala Frigerio, Steffen Jung, Soyon Hong
Summary: Microglia mediate aberrant synapse engulfment in Alzheimer's disease (AD), but the underlying mechanisms are poorly understood. Here the authors show a perivascular cells-to-microglia crosstalk that induces microglia phagocytic state resulting in synapse engulfment in two mouse models of AD.
NATURE NEUROSCIENCE
(2023)
Correction
Neurosciences
Mor Kenigsbuch, Pierre Bost, Shahar Halevi, Yuzhou Chang, Shuo Chen, Qin Ma, Renana Hajbi, Benno Schwikowski, Bernd Bodenmiller, Hongjun Fu, Michal Schwartz, Ido Amit
NATURE NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Junil Kim, Michaela Mrugala Rothova, Esha Madan, Siyeon Rhee, Guangzheng Weng, Antonio M. Palma, Linbu Liao, Eyal David, Ido Amit, Morteza Chalabi Hajkarim, Vignesh Vudatha, Andres Gutierrez-Garcia, Eduardo Moreno, Robert Winn, Jose Trevino, Paul B. Fisher, Joshua M. Brickman, Rajan Gogna, Kyoung Jae Won
Summary: Development of multicellular organisms relies on persistent cell-cell communication, which drives lineage specification and cell fate decisions. The current single-cell RNA-seq technology lacks spatial information needed to analyze cell-cell contact-dependent gene expression. To overcome this, we performed RNA sequencing of physically interacting cells (PIC-seq) and compared them with single-cell transcriptomes from developing mouse embryos. Our analysis identified cell-type-dependent gene expression signatures, and we developed a computational model to predict the impact of one cell type on neighboring cell types. We also developed a spatial embedding method to visualize the distribution of cells in a 2D space. This innovative approach allows us to study contact-specific gene regulation during embryogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Jennifer Cable, Jeffrey C. Rathmell, Erika L. Pearce, Ping-Chih Ho, Marcia C. Haigis, Murad R. Mamedov, Meng-Ju Wu, Susan M. Kaech, Lydia Lynch, Mark A. Febbraio, Sagar P. Bapat, Hanna S. Hong, Weiping Zou, Yasmine Belkaid, Zuri A. Sullivan, Andrea Keller, Stefanie K. Wculek, Douglas R. Green, Catherine Postic, Ido Amit, Salvador Aznar Benitah, Russell G. Jones, Miguel Reina-Campos, Santiago Valle Torres, Semir Beyaz, Donal Brennan, Luke A. J. O'Neill, Rachel J. Perry, Dirk Brenner
Summary: Immunometabolism studies the relationship between metabolism and immunity, with a focus on the metabolic pathways within immune cells and the impact of immune cells on systemic metabolism. In the Keystone symposium on Immunometabolism at the Crossroads of Obesity and Cancer, experts presented recent research on the complex interplay between metabolism, immunity, and cancer, highlighting metabolic links between tumor cells and immune cells, the effects of diet, the microbiome, and obesity on immune system function and cancer, and new technologies to study the immune system and uncover novel metabolic pathways.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Cell Biology
Svetlana Markman, Mor Zada, Eyal David, Amir Giladi, Ido Amit, Elazar Zelzer
Summary: Through single-cell RNA sequencing of developing mouse forelimb, we identify three progenitor states: naive, proximal, and autopodial, with Msx1 as a marker for naive progenitors. Lineage tracing confirms the role of naive progenitors and locates them at the outer margin of the limb along the anterior-posterior axis. Sequential pulse-chase experiments show that the progressive transition of Msx1+ naive progenitors into proximal and autopodial progenitors coincides with their differentiation into Sox9+ chondroprogenitors, occurring along all the forming skeletal segments. Hence, the skeleton forms progressively in a complex pattern.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Bjort K. Kragesteen, Amir Giladi, Eyal David, Shahar Halevi, Laufey Geirsdottir, Olga M. Lempke, Baoguo Li, Andreas M. Bapst, Ken Xie, Yonatan Katzenelenbogen, Sophie L. Dahl, Fadi Sheban, Anna Gurevich-Shapiro, Mor Zada, Truong San Phan, Roberto Avellino, Shuang-Yin Wang, Oren Barboy, Shir Shlomi-Loubaton, Sandra Winning, Philipp P. Markwerth, Snir Dekalo, Hadas Keren-Shaul, Merav Kedmi, Martin Sikora, Joachim Fandrey, Thorfinn S. Korneliussen, Josef T. Prchal, Barak Rosenzweig, Vladimir Yutkin, Fernando Racimo, Eske Willerslev, Chamutal Gur, Roland H. Wenger, Ido Amit
Summary: Single-cell RNA and transposase-accessible chromatin (ATAC) sequencing in a mouse model identified a rare cell subset called Norn cells in kidney stroma as the major source of endocrine Epo production in mice, and this finding was confirmed in human kidney tissues. These findings provide new insights into EPO gene regulation and may lead to improved therapies for anemia.
Article
Multidisciplinary Sciences
Sara Caxaria, Sabah Bharde, Alice M. Fuller, Romy Evans, Bethan Thomas, Petek Celik, Francesco Dell'Accio, Simon Yona, Derek Gilroy, Mathieu-Benoit Voisin, John N. Wood, Shafaq Sikandar
Summary: We demonstrated the role of neutrophils in fibromyalgia by using a back-translational approach in mice. Adoptive transfer of neutrophils from mice with chronic widespread pain or patients with fibromyalgia can induce mechanical pain in recipient mice, sensitize spinal cord neurons, and cause changes in the expression of neutrophil proteins that lead to neutrophil infiltration into dorsal root ganglia. These findings suggest an immunological basis for chronic widespread pain in fibromyalgia mediated by neutrophils.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Thomas Look, Emanuele Puca, Marcel Buhler, Daniel Kirschenbaum, Roberto De Luca, Riccardo Stucchi, Domenico Ravazza, Cesare Di Nitto, Patrick Roth, Yonatan Katzenelenbogen, Assaf Weiner, Lukas Rindlisbacher, Burkhard Becher, Ido Amit, Michael Weller, Dario Neri, Teresa Hemmerle, Tobias Weiss
Summary: In this study, a combination therapy of L19TNF, an antibody-cytokine fusion protein, and CCNU, an alkylating agent, demonstrated strong anti-glioma activity in mouse models. The combination treatment induced tumor DNA damage, tumor necrosis, up-regulation of tumor endothelial cell adhesion molecules, immune cell infiltration, immunostimulatory pathways, and decreased immunosuppression pathways. Clinical translation of this combination therapy in glioblastoma patients has shown objective responses in a patient cohort, indicating its potential efficacy.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Omer Goldman, Lital N. Adler, Emma Hajaj, Tommaso Croese, Naama Darzi, Sivan Galai, Hila Tishler, Yarden Ariav, Dor Lavie, Liat Fellus-Alyagor, Roni Oren, Yuri Kuznetsov, Eyal David, Rami Jaschek, Chani Stossel, Oded Singer, Sergey Malitsky, Renana Barak, Rony Seger, Neta Erez, Ido Amit, Amos Tanay, Ann Saada, Talia Golan, Tamar Rubinek, Joo Sang Lee, Shay Ben-Shachar, Ido Wolf, Ayelet Erez
Summary: Multiple studies have found metabolic changes within the tumor and its micro-environment during carcinogenesis, but the mechanisms by which tumors affect the host metabolism are unclear. This study discovered that systemic inflammation induced by cancer results in the infiltration of myeloid cells into the liver, leading to the depletion of a master metabolic regulator, HNF4α, and subsequently causing systemic metabolic changes that promote breast and pancreatic cancer proliferation.
Review
Neurosciences
Gal Ronit Frumer, Sun-Hye Shin, Steffen Jung, Jung-Seok Kim
Summary: This article reviews recent advances in our understanding of brain macrophage heterogeneity, including microglia and border-associated macrophages, with a focus on the mouse. The strengths and limitations of the experimental approaches are discussed, which have provided new insights and hold promise for further understanding the mechanisms of brain macrophages and potentially harnessing their activities for CNS pathology management.