Article
Biochemistry & Molecular Biology
Alaa Alsalloum, Saleh Alrhmoun, Julia Shevchenko, Marina Fisher, Julia Philippova, Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Julia Lopatnikova, Vasily Kurilin, Marina Volynets, Yasushi Akahori, Hiroshi Shiku, Alexander Silkov, Sergey Sennikov
Summary: This study investigates the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. The cytotoxicity and functional characteristics of these modified T cells, as well as immune transcriptome profiling and multiplex immunoassays, demonstrate their promising therapeutic potential for cancer treatment.
Article
Multidisciplinary Sciences
Charlotte A. James, Yuexin Xu, Melissa S. Aguilar, Lichen Jing, Erik D. Layton, Martine Gilleron, Adriaan J. Minnaard, Thomas J. Scriba, Cheryl L. Day, Edus H. Warren, David M. Koelle, Chetan Seshadri
Summary: This study reveals the importance of CD4 and CD8 co-receptors in recognizing mycobacterial glycolipid antigens. The expression of either CD4 or CD8 increases the avidity of T cell receptors for mycolipids, leading to a higher intensity of fluorescence and decreased secretion threshold for interferon-gamma. Furthermore, CD8+ T cells show greater cytotoxicity compared to CD4+ T cells in individuals with active tuberculosis.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Segi Kim, Cho I. Park, Sunhwa Lee, Hyeong Ryeol Choi, Chan Hyuk Kim
Summary: This study used CRISPR/Cas9 gene editing technology to insert the interleukin-12 (IL-12) gene into the programmed cell death 1 (PDCD1) locus, achieving T-cell activation-dependent expression of IL-12 and inhibition of PD-1 expression. The results showed that this method of inducible IL-12 expression from the PDCD1 locus enhances anti-tumor effects with lower risk of adverse effects, providing a new approach for the development of effective adoptive T cell therapies against solid tumors.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Eunhee Kim, Dong Min Lee, Min Ji Seo, Hong Jae Lee, Kyeong Sook Choi
Summary: Paraptosis is a type of programmed cell death characterized by dilation of the endoplasmic reticulum and/or mitochondria. Ca2+ transport has been shown to play an important role in paraptosis induced by various agents, and perturbations of cellular proteostasis and ion homeostasis are believed to contribute critically to the process. The communication between the ER and mitochondria mediated by Ca2+ appears to be crucial in inducing paraptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Nan Wang, Chong Wang, Hongyang Zhao, Yichun He, Beiwu Lan, Liankun Sun, Yufei Gao
Summary: The cooperation and antagonism between organelles within the cell play a crucial role in maintaining cellular homeostasis. The signaling crosstalk between the endoplasmic reticulum (ER) and mitochondria influences cell fate. Mitochondria-associated membranes (MAMs) are pivotal in regulating lipid synthesis, calcium homeostasis, ER-mitochondrial coordination, and death signal transduction, contributing to cell death mechanisms such as apoptosis.
Article
Cell Biology
Benjamin Cartes-Saavedra, Josefa Macuada, Daniel Lagos, Duxan Arancibia, Maria E. Andres, Patrick Yu-Wai-Man, Gyoergy Hajnoczky, Veronica Eisner
Summary: Autosomal Dominant Optic Atrophy (ADOA), caused by OPA1 mutations, affects Ca2+ homeostasis by modulating ER-mitochondria coupling, potentially contributing to the progression of ADOA.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Thamotharampillai Dileepan, Deepali Malhotra, Dmitri I. Kotov, Elizabeth M. Kolawole, Peter D. Krueger, Brian D. Evavold, Marc K. Jenkins
Summary: Engineered peptide:MHCII tetramers with enhanced CD4 binding outperform traditional tetramers in detecting antigen-specific CD4(+) T cells, allowing for identification of more T cells in immunized mice. These new reagents provide a deeper understanding of the T cell repertoire.
NATURE BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Shanliang Zheng, Dong Zhao, Guixue Hou, Song Zhao, Wenxin Zhang, Xingwen Wang, Li Li, Liang Lin, Tie-Shan Tang, Ying Hu
Summary: The study demonstrates the interaction between TMCO1 and iASPP in colon cancer, affecting tumor growth and cell apoptosis by modulating Ca2+ homeostasis. Intervention in the iASPP-TMCO1 axis can effectively inhibit tumor progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Physiology
Lianguo Wang, Rachel C. Myles, I-Ju Lee, Donald M. Bers, Crystal M. Ripplinger
Summary: The study demonstrates that inhibition of SERCA can slow down SR Ca2+ reuptake, leading to an increase in the magnitude of Ca2+ alternans in cardiac cells, especially at fast pacing frequencies. Notably, the alternation of SR Ca2+ release precedes the alternation of SR Ca2+ load during rapid ventricular pacing.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Neurosciences
Mohammad A. Ghane, Wei Wei, Dina W. Yakout, Zachary D. Allen, Cassandra L. Miller, Bin Dong, Jenny J. Yang, Ning Fang, Angela M. Mabb
Summary: The study found that disrupting Arc protein ubiquitination enhances DHPG-induced ER-mediated Ca2+ release. This alteration is observed in all neuronal subregions except secondary branchpoints. Disruptions in Arc ubiquitination increase Arc interaction with the integral ER protein Calnexin.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Jinhong Wei, Wenting Guo, Ruiwu Wang, John Paul Estillore, Darrell Belke, Yong-Xiang Chen, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, S. R. Wayne Chen
Summary: The physiological significance of PKA phosphorylation of RyR2 in the heart is still poorly understood. Recent structural studies have shown that the PKA phosphorylation site S2030 in RyR2 is located within a pathway that is important for the termination of Ca2+ release. We investigated the impact of S2030 mutations on Ca2+ release termination in cells and generated a mouse model to study the role of S2030 in a physiological setting.
CIRCULATION RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Xintong Bian, Ningke Fan, Meng Li, Daobin Han, Jia Li, Lu Fan, Xinyu Li, Liangsheng Kong, Hua Tang, Shijia Ding, Fangzhou Song, Siqiao Li, Wei Cheng
Summary: A hepatocellular carcinoma (HCC) cell-derived ER vesicle (ER-horse) has been developed for precise HCC nanotherapy by imitating the physiological function of endoplasmic reticulum (ER) and triggering excessive ER stress and apoptosis. The findings provide a new method for HCC nanotherapy via interference of ER stress signaling.
Article
Oncology
Xin Liu, Yixiang Xu, Wei Xiong, Bingnan Yin, Yuqian Huang, Junjun Chu, Changsheng Xing, Chen Qian, Yang Du, Tianhao Duan, Helen Y. Wang, Ningyan Zhang, John S. Yu, Zhiqiang An, Rongfu Wang
Summary: This study developed a TCR-like antibody and CAR-T cells to recognize intracellular proteins as a target for cancer immunotherapy. The specificity and antitumor activity of the antibody and CAR-T cells were demonstrated both in vitro and in vivo, providing a novel approach for the development of cancer immunotherapeutics.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Yusuf Dolen, Uzi Gileadi, Ji-Li Chen, Michael Valente, Jeroen H. A. Creemers, Eric A. W. Van Dinther, N. Koen van Riessen, Eliezer Jager, Martin Hruby, Vincenzo Cerundolo, Mustafa Diken, Carl G. Figdor, I. Jolanda M. de Vries
Summary: A PLGA-based nanoparticle vaccine containing immunogenic cancer germline antigen NY-ESO-1 and iNKT cell agonist was developed, which efficiently induced antigen-specific T cell responses in vivo without systemic toxicity at high doses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Lauren C. Panzera, Ben Johnson, Josiah A. Quinn, In Ha Cho, Michael M. Tamkun, Michael B. Hoppa
Summary: Research indicates that Kv2.1 channels play a crucial role in facilitating ER calcium uptake during electrical activity in neurons, which is related to synaptic transmission. Loss of the Kv2.1 channel can disrupt synaptic vesicle fusion during stimulation, while its non-conducting role can link ER calcium uptake with electrical activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Cell Biology
Antony Galione, Lianne C. Davis, Anthony J. Morgan
Summary: LC3-lipidation is activated by mechanisms unrelated to canonical autophagy, as this study shows that lysosomal damage induced by lysosomotropic agents or oxalate leads to TFEB dephosphorylation and translocation into the nucleus which promotes the clearance of damaged lysosomes, reducing the deleterious effects of crystal nephmpathy.
Article
Cell Biology
Anthony J. Morgan, Antony Galione
Summary: Pharmacological manipulation that disrupts lysosome membrane integrity or ionic movements can inhibit store-operated calcium entry (SOCE) by uncoupling the release of calcium from the endoplasmic reticulum. Certain agents inducing lysosomal membrane permeabilization interfere with SOCE through Stim1 oligomerization and activation of Orai, while others like the K+/H+ ionophore inhibit SOCE in a Stim1-dependent manner. Other lysosomal manipulation strategies do not affect SOCE, and the effects of lysosomal agents on SOCE can be reversed by a dynamin inhibitor.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Tiphaine Douanne, Jane C. Stinchcombe, Gillian M. Griffiths
Summary: Immune synapses play a crucial role in communication and immune response coordination among immune cells, bearing resemblance to cellular structures responsible for signaling and secretion. Studies have revealed morphological, functional, and molecular similarities between immune synapses and primary cilia, with ongoing comparative research shedding light on their underlying molecular mechanisms.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Mathew Clement, Lea Knezevic, Tamsin Dockree, James E. McLaren, Kristin Ladell, Kelly L. Miners, Sian Llewellyn-Lacey, Anzelika Rubina, Ore Francis, David K. Cole, Andrew K. Sewell, John S. Bridgeman, David A. Price, Hugo A. van den Berg, Linda Wooldridge
Summary: This study investigates how CD8(+) T cells modulate antigen sensitivity through interactions with MHCI and CD8, showing that this interaction can reorder the agonist hierarchy of peptide ligands with different affinities for the TCR.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Veronica Martini, Matthew Edmans, Simon Gubbins, Siddharth Jayaraman, Basudev Paudyal, Sophie Morgan, Adam McNee, Theo Morin, Pramila Rijal, Wilhelm Gerner, Andrew K. Sewell, Ryo Inoue, Mick Bailey, Timothy Connelley, Bryan Charleston, Alain Townsend, Peter Beverley, Elma Tchilian
Summary: This study investigates the distribution of porcine CD8 T cells in lymphoid and respiratory tissues after influenza infection or immunization. Different types of CD8 T cells were defined and analyzed. The expression of influenza-specific memory CD8 T cells varies in different tissues and declines to background levels after 63 days.
MUCOSAL IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anthony J. Morgan, Lora L. Martucci, Lianne C. Davis, Antony Galione
Summary: In recent years, there has been a significant progress in understanding the structure, mechanisms and functions of the endo-lysosomal TPC family. TPCs play integral roles in fundamental signal-transduction pathways, with their diverse cation conductances allowing them to signal electrically, osmotically or chemically. Their distribution in different tissues and organelles, together with their selective ion permeabilities, make them important mediators in immunity, cancer, metabolism, viral infectivity and neurodegeneration.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Garry Dolton, Cristina Rius, Md Samiul Hasan, Aaron Wall, Barbara Szomolay, Enas Behiry, Thomas Whalley, Joel Southgate, Anna Fuller, Theo Morin, Katie Topley, Li Rong Tan, Philip J. R. Goulder, Owen B. Spiller, Pierre J. Rizkallah, Lucy C. Jones, Thomas R. Connor, Andrew K. Sewell
Summary: This study examined the CD8 T cell response against a specific epitope of the Spike glycoprotein of SARS-CoV-2 and found that a specific mutation was not recognized by the majority of HLA A*02(+) convalescent patients and vaccinated individuals. This highlights the potential problem of viral escape at prevalent T cell epitopes restricted by high frequency HLAs and suggests the inclusion of multiple viral proteins in next generation vaccines. Monitoring T cell escape in new SARS-CoV-2 variants is crucial.
Letter
Biochemical Research Methods
Mikhail Goncharov, Dmitry Bagaev, Dmitrii Shcherbinin, Ivan Zvyagin, Dmitry Bolotin, Paul G. Thomas, Anastasia A. Minervina, Mikhail V. Pogorelyy, Kristin Ladell, James E. McLaren, David A. Price, Thi H. O. Nguyen, Louise C. Rowntree, E. Bridie Clemens, Katherine Kedzierska, Garry Dolton, Cristina Rafael Rius, Andrew Sewell, Jerome Samir, Fabio Luciani, Ksenia V. Zornikova, Alexandra A. Khmelevskaya, Saveliy A. Sheetikov, Grigory A. Efimov, Dmitry Chudakov, Mikhail Shugay
Article
Multidisciplinary Sciences
Yuzhe Weng, Dawn Shepherd, Yi Liu, Nitya Krishnan, Brian D. Robertson, Nick Platt, Gerald Larrouy-Maumus, Frances M. Platt
Summary: Lipids shed by pathogenic mycobacteria inhibit the NPC1 pathway, which is crucial for the evolution of pathogenicity and disease progression.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biology
Laura Rivino, Linda Wooldridge
Summary: Activated T cells from a previous herpesvirus infection can also recognize and respond to SARS-CoV-2, irrespective of when the herpesvirus infection occurred.
Article
Immunology
Alice Halliday, Anna E. Long, Holly E. Baum, Amy C. Thomas, Kathryn L. Shelley, Elizabeth Oliver, Kapil Gupta, Ore Francis, Maia Kavanagh Williamson, Natalie Di Bartolo, Matthew J. Randell, Yassin Ben-Khoud, Ilana Kelland, Georgina Mortimer, Olivia Ball, Charlie Plumptre, Kyla Chandler, Ulrike Obst, Massimiliano Secchi, Lorenzo Piemonti, Vito Lampasona, Joyce Smith, Michaela Gregorova, Lea Knezevic, Jane Metz, Rachael Barr, Begonia Morales-Aza, Jennifer Oliver, Lucy Collingwood, Benjamin Hitchings, Susan Ring, Linda Wooldridge, Laura Rivino, Nicholas Timpson, Jorgen McKernon, Peter Muir, Fergus Hamilton, David Arnold, Derek N. Woolfson, Anu Goenka, Andrew D. Davidson, Ashley M. Toye, Imre Berger, Mick Bailey, Kathleen M. Gillespie, Alistair J. K. Williams, Adam Finn
Summary: Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings with limited active testing. The study developed and evaluated multiple antibody detection methods, demonstrating that low-volume in-house assays provide good diagnostic performance and better sensitivity than a commercial assay.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Christopher M. Rice, Philip Lewis, Fernando M. Ponce-Garcia, Willem Gibbs, Sarah Groves, Drinalda Cela, Fergus Hamilton, David Arnold, Catherine Hyams, Elizabeth Oliver, Rachael Barr, Anu Goenka, Andrew Davidson, Linda Wooldridge, Adam Finn, Laura Rivino, Borko Amulic
Summary: Neutrophil activity and phenotypic diversity vary in COVID-19 patients. Severe cases exhibit hyperactivation of immature CD102 subpopulations, indicating increased secondary granule release. Partially activated immature neutrophils are detectable in convalescent patients, suggesting long-term myeloid dysregulation. Neutrophils from moderately ill patients down-regulate CXCR2, while those from severely ill individuals fail to do so, potentially influencing organ trafficking and disease tolerance. CD102 and CXCR2hi neutrophil subpopulations may serve as prognostic biomarkers for identifying individuals at high risk of severe COVID-19.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Garry Dolton, Cristina Rius, Aaron Wall, Barbara Szomolay, Valentina Bianchi, Sarah A. E. Galloway, Md Samiul Hasan, Theo Morin, Marine E. Caillaud, Hannah L. Thomas, Sarah Theaker, Li Rong Tan, Anna Fuller, Katie Topley, Mateusz Legut, Meriem Attaf, Jade R. Hopkins, Enas Behiry, Joanna Zabkiewicz, Caroline Alvares, Angharad Lloyd, Amber Rogers, Peter Henley, Christopher Fegan, Oliver Ottmann, Stephen Man, Michael D. Crowther, Marco Donia, Inge Marie Svane, David K. Cole, Paul E. Brown, Pierre Rizkallah, Andrew K. Sewell
Summary: Tumor-infiltrating lymphocyte therapy can activate T cells of the immune system to target and eliminate solid cancers. Through the use of combinatorial peptide libraries and a proteomic database, the antigen specificities of persistent cancer-specific T cell receptors (TCRs) were identified after successful therapy for stage IV malignant melanoma. These TCRs were capable of targeting multiple tumor types through specific epitopes, and the atomic structures revealed the importance of a shared recognition motif. The ability of these multi-epitope targeting T cells to recognize cancer cells surpasses the recognition of individual epitopes, making them promising candidates for future immunotherapies.
Article
Cell Biology
Yuan Chen, Georgina H. Mason, D. Oliver Scourfield, Alexander Greenshields-Watson, Tracey A. Haigh, Andrew K. Sewell, Heather M. Long, Awen M. Gallimore, Pierre Rizkallah, Bruce J. MacLachlan, Andrew Godkin
Summary: CD4+ T cells recognize a diverse range of SARS-CoV-2 peptide epitopes, contributing to immune memory and limiting COVID-19 disease. The immunogenicity of these peptides does not correlate with their binding affinity to HLA-DR1. X-ray crystallographic structures of six epitopes bound to HLA-DR1 reveal the molecular impact of viral variant mutations on epitope presentation. Omicron variant escapes immune recognition through mutations in TCR-facing epitope positions and a single amino acid substitution that alters the peptide-HLA structure.