Article
Biology
Victoria L. Czech, Lauren C. O'Connor, Brendan Philippon, Emily Norman, Alexandra B. Byrne
Summary: TIR-1/dSarm/SARM1, a key regulator of axon degeneration, inhibits axon regeneration while promoting axon degeneration by interacting with different MAP kinase pathways. This mechanism is conserved in human SARM1. These findings provide critical insight into the multidimensional regulation of axon injury response and may inform strategies for repair.
Article
Multidisciplinary Sciences
Alexander M. Hilla, Annemarie Baehr, Marco Leibinger, Anastasia Andreadaki, Dietmar Fischer
Summary: Regenerative failure in the optic nerve is attributed to a chemoattractive CXCL12/CXCR4-dependent mechanism that prevents growth-stimulated axons from regenerating distally. Depletion of CXCR4 or CXCL12 reduces aberrant axonal growth and enables long-distance regeneration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Min Jung Kwon, Yeojin Seo, Hana Cho, Hyung Soon Kim, Young Joo Oh, Simay Geniscan, Minjae Kim, Hee Hwan Park, Eun-Hye Joe, Myung-Hee Kwon, Han Chang Kang, Byung Gon Kim
Summary: Preconditioning nerve injury can enhance axonal regeneration of DRG neurons by activating pro-regenerative perineuronal macrophages. This study reveals that oncomodulin (ONCM) produced from regeneration-associated macrophages strongly influences the regeneration of DRG sensory axons. Delivery of ONCM using a nanogel system can promote sensory axon regeneration following spinal cord injury.
Article
Neurosciences
Yu-Fen Liu, Jia-Jian Liang, Tsz Kin Ng, Zhanchi Hu, Ciyan Xu, Shaowan Chen, Shao-Lang Chen, Yanxuan Xu, Xi Zhuang, Shaofen Huang, Mingzhi Zhang, Chi Pui Pang, Ling-Ping Cen
Summary: This study found that the CXCL5/CXCR2 pathway promotes RGC survival and axonal regeneration after optic nerve injury, with CXCL5 enhancing RGC protection and axonal regeneration. These findings suggest that CXCL5/CXCR2 could be a potential therapeutic target for promoting RGC survival after ON injury.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yu-Jih Su, Pei-Wen Wang, Shao-Wen Weng
Summary: The role of mitochondria in the immune system is crucial, providing energy, activating cells, and playing a key role in tissue regeneration and aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
M. Clement, J. L. Forbester, M. Marsden, P. Sabberwal, M. S. Sommerville, D. Wellington, S. Dimonte, S. Clare, K. Harcourt, Z. Yin, L. Nobre, R. Antrobus, B. Jin, M. Chen, S. Makvandi-Nejad, J. A. Lindborg, S. M. Strittmatter, M. P. Weekes, R. J. Stanton, T. Dong, I. R. Humphreys
Summary: IFITM3 restricts viral pathogenesis by regulating Nogo-B-mediated inflammatory response, not only in response to cytomegalovirus but also to influenza and SARS-CoV-2.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Qiuyue Ma, Roland Immler, Monika Pruenster, Markus Sellmayr, Chenyu Li, Albrecht von Brunn, Brigitte von Brunn, Rosina Ehmann, Roman Woelfel, Matteo Napoli, Qiubo Li, Paola Romagnani, Ralph Thomas Boettcher, Markus Sperandio, Hans-Joachim Anders, Stefanie Steiger
Summary: This study investigates the impact of uric acid on neutrophils and finds that hyperuricemia impairs neutrophil function. Partial reduction of uric acid levels using uricase can partially restore the neutrophil defects. The study reveals that uric acid affects neutrophil migration by regulating intracellular pH and cytoskeletal dynamics. These findings have important implications for understanding immunodeficiency in kidney disease and sterile inflammation.
Article
Hematology
Peter A. A. Norris, Gurleen Kaur, Ramsha Khan, Guangheng Zhu, Heyu Ni, Alan H. Lazarus
Summary: Anti-CD44 exhibits anti-inflammatory effects in murine ITP by inhibiting macrophage phagocytosis through blockade of Fc gamma R, potentially serving as an alternative to IVIg. The specific Fc gamma R blockade mechanism of anti-CD44 contributes to its therapeutic efficacy in ITP models, highlighting its potential as a treatment option.
Review
Biochemistry & Molecular Biology
Filippo Pinelli, Fabio Pizzetti, Valeria Veneruso, Emilia Petillo, Michael Raghunath, Giuseppe Perale, Pietro Veglianese, Filippo Rossi
Summary: Spinal cord injury is a damaging process that occurs during an acute traumatic event, and requires a multi-target approach for treatment. Recent advances in biomaterials and drug/biomolecule combinations have shown promise in the treatment of spinal cord injuries.
Article
Biology
Ziwei Yang, Jun Wang, Bailin He, Xiaolin Zhang, Xiaojuan Li, Ersheng Kuang
Summary: This study demonstrates that RTN3 acts as a negative regulator of immune and inflammatory responses during RNA viral infection by impairing K63-linked polyubiquitination of IRF3 and NF-kappa B. Overexpression of RTN3 in mice results in decreased neutrophil numbers and inflammatory cell infiltration, indicating its role in resolving inflammation.
Article
Neurosciences
Maria Savvaki, George Kafetzis, Stefanos-Ioannis Kaplanis, Niki Ktena, Kostas Theodorakis, Domna Karagogeos
Summary: In the murine optic nerve crush model, neuronal and glial CNTN2 play distinct roles in regenerative responses. Neuronal CNTN2 acts as a negative regulator of axon regeneration by inhibiting the Akt signaling pathway, while glial CNTN2 and hypomyelination are dispensable for both neuronal survival and axon regeneration.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biology
Yingzhi Gu, Yang Hu, Shengyuan Huang, Sunniva Ruiz, Toshihisa Kawai, Yuxing Bai, Xiaozhe Han
Summary: The controlled delivery of immunomodulatory biologicals can regulate the regeneration of alveolar bone by promoting anti-inflammatory response, inhibiting bone resorption, and promoting new bone deposition. The incorporation of cytosine-phosphate-guanosine oligodeoxynucleotides and glucosylxanthone Mangiferin into hydrogel microbeads demonstrated promising results in promoting alveolar bone regeneration. This study provides a potential therapeutic strategy for the treatment of alveolar bone regeneration.
Article
Plant Sciences
Haojia Wang, Xin Jia, Meiqi Zhang, Cuiqin Cheng, Xue Liang, Xuejiao Wang, Fang Xie, Jinyong Wang, Yanli Yu, Yuting He, Qiutong Dong, Yao Wang, Anlong Xu
Summary: Isoliquiritigenin (ISL), a natural NRF2 agonist, exhibits antiviral and anti-inflammatory effects against VSV, H1N1, EMCV, and HSV-1 by activating NRF2 signaling.
Article
Biochemistry & Molecular Biology
Ying Zhou, Peter J. Little, Suowen Xu, Danielle Kamato
Summary: Curcumin, a natural compound widely used in Asian countries, has anti-inflammatory and anti-oxidative properties. Researchers have found that curcumin can prevent atherosclerosis by blocking ROCK signaling pathway.
Article
Multidisciplinary Sciences
Di Liu, Zhiyao Zhao, Yuanchu She, Lei Zhang, Xiangtian Chen, Ling Ma, Jun Cui
Summary: The study identifies TRIM14 as an epigenetic regulator that modulates the immune response by inhibiting the autophagic degradation of the histone demethylase KDM4D. TRIM14 deficiency in dendritic cells impairs the expression of proinflammatory cytokines and protects mice from autoimmune inflammation, suggesting TRIM14 as a potential therapeutic target for inflammation-related diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Khiyam Hussain, Rena Liu, Rosanna C. G. Smith, Kri T. J. Muller, Mohammadmersad Ghorbani, Sofia Macari, Kirstie L. S. Cleary, Robert J. Oldham, Russell B. Foxall, Sonya James, Steven G. Booth, Tom Murray, Lekh N. Dahal, Chantal E. Hargreaves, Robert S. Kemp, Jemma Longley, James Douglas, Hannah Markham, Serena J. Chee, Richard J. Stopforth, Ali Roghanian, Matthew J. Carter, Christian H. Ottensmeier, Bjorn Frendeus, Ramsey Cutress, Ruth R. French, Martin J. Glennie, Jonathan C. Strefford, Stephen M. Thirdborough, Stephen A. Beers, Mark S. Cragg
Summary: Hypoxia in the tumor microenvironment can upregulate the expression of Fc gamma RIIb receptors on tumor-associated macrophages (TAMs), which leads to reduced antibody dependent cellular phagocytosis (ADCP) and decreased efficacy of monoclonal antibody (mAb) immunotherapy. This finding provides a mechanistic basis for targeting Fc gamma RIIb expression or blocking it as a promising strategy for enhancing mAb immunotherapies.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Ninel Miriam Vainshelbaum, Kristine Salmina, Bogdan I. Gerashchenko, Marija Lazovska, Pawel Zayakin, Mark Steven Cragg, Dace Pjanova, Jekaterina Erenpreisa
Summary: In this review, the role of the circadian clock (CC) in cancer cells' resistance to genotoxic treatments is discussed, particularly in relation to whole-genome duplication (WGD) and telomere-length regulation. The deregulation of the CC in cancer cells leads to alterations in cell cycle progression and DNA damage response, allowing cancer cells to evade genotoxic treatments and prolong their survival. The review highlights the correlation between cancer WGD and CC deregulation and proposes a mechanism involving polyploidy and the CC death loop. This review provides insights into the lifecycle of cancer and suggests the potential of cancer treatment by differentiation.
Article
Biology
Franziska Heckel, Anna H. Turaj, Hayden Fisher, H. T. Claude Chan, Michael J. E. Marshall, Osman Dadas, Christine A. Penfold, Tatyana Inzhelevskaya, C. Ian Mockridge, Diego Alvarado, Ivo Tews, Tibor Keler, Stephen A. Beers, Mark S. Cragg, Sean H. Lim
Summary: Agonistic CD27 monoclonal antibodies can enhance the efficacy of depleting antibodies such as anti-CTLA-4; the agonism of CD27 antibody depends on isotype and epitope specificity; Fc-engineering can improve the agonism of CD27 monoclonal antibodies.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Alexander P. Simpson, Ali Roghanian, Robert J. Oldham, H. T. Claude Chan, Christine A. Penfold, Hyung J. Kim, Tatyana Inzhelevskaya, C. Ian Mockridge, Kerry L. Cox, Yury D. Bogdanov, Sonya James, Alison L. Tutt, Daniel Rycroft, Peter Morley, Lekh N. Dahal, Ingrid Teige, Bjorn Frendeus, Stephen A. Beers, Mark S. Cragg
Summary: This study demonstrates that hFcyRIIB can inhibit effector cell function and immunotherapy by competing with activating FcyRs for antibody Fc, rather than through ITIM signaling.
Article
Immunology
Christian M. Orr, Hayden Fisher, Xiaojie Yu, Claude H-T Chan, Yunyun Gao, Patrick J. Duriez, Steven G. Booth, Isabel Elliott, Tatyana Inzhelevskaya, Ian Mockridge, Christine A. Penfold, Armin Wagner, Martin J. Glennie, Ann L. White, Jonathan W. Essex, Arwen R. Pearson, Mark S. Cragg, Ivo Tews
Summary: Hinge disulfide orientation in the IgG2 isotype affects its agonistic activity by modulating receptor signaling. Crystallographic structures reveal a disulfide crossover between F(ab) arms in agonistic forms, independent of epitope. The least flexible variants induce the highest levels of receptor agonism.
SCIENCE IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaojie Yu, Christian M. Orr, H. T. Claude Chan, Sonya James, Christine A. Penfold, Jinny Kim, Tatyana Inzhelevskaya, C. Ian Mockridge, Kerry L. Cox, Jonathan W. Essex, Ivo Tews, Martin J. Glennie, Mark S. Cragg
Summary: Low affinity of immunomodulatory antibodies leads to greater activity through increased clustering, resulting in higher immune cell activation, T cell expansion, and antitumor activity. This discovery reveals a new mechanism for enhancing receptor activation across diverse receptor families and sheds light on the mechanism of antibody-mediated receptor signaling. Affinity engineering offers a rational, efficient, and tunable solution for delivering antibody-mediated receptor activity for the treatment of human disease.
Article
Biochemistry & Molecular Biology
Kristine Salmina, Ninel Miriam Vainshelbaum, Madara Kreishmane, Inna Inashkina, Mark Steven Cragg, Dace Pjanova, Jekaterina Erenpreisa
Summary: In our study, we found that triple-negative breast cancer MDA-MB-231 cells become resistant to doxorubicin treatment by discarding damaged DNA during mitotic slippage. We observed two populations of polyploid giant cells, one producing surviving offspring and the other reaching high ploidy and persisting for weeks. The origin and relationship of these two sub-populations in the context of mitotic slippage were characterized. The emergence of nuclear markers indicating a soma-germ transition was observed during mitotic slippage, and there was a link between inflammatory innate immune response and placenta developmental genes in polyploid giant cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Osman Dadas, Ayse Ertay, Mark S. Cragg
Summary: The tumor necrosis factor superfamily and their receptors play important roles in regulating the immune system. Targeting these receptors for immunotherapy shows promise, but challenges remain in translating successful pre-clinical studies into clinical applications. This review discusses the importance of co-stimulatory members of the receptor family, the rationale for targeting them in immunotherapy, and the development of next generation agents to overcome limitations and provide effective and safe drugs for patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Jekaterina Erenpreisa, Alessandro Giuliani, Mark Steven Cragg
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Jack G. Fisher, Amber D. P. Doyle, Lara V. Graham, Shreyanshi Sonar, Ben Sale, Isla Henderson, Luis Del Rio, Peter W. M. Johnson, Yosef Landesman, Mark S. Cragg, Francesco Forconi, Christopher J. Walker, Salim. I. Khakoo, Matthew D. Blunt
Summary: The XPO1 inhibitor selinexor is being investigated in combination with the BTK inhibitor ibrutinib for CLL and non-Hodgkin lymphoma. Selinexor induces apoptosis of tumor cells and modulates NK cell and T cell cytotoxicity against lymphoma cells.
Review
Immunology
Falk Nimmerjahn, Gestur Vidarsson, Mark S. Cragg
Summary: Humoral immune responses generate polyclonal antibodies with varied isotypes, epitope specificity, and affinity. Posttranslational modifications in antibody variable and constant domains can modify antigen specificity and antibody Fc-dependent functions. Understanding the impact of these modifications on antibody function is still limited, but it has implications for therapeutic antibody development. This Review provides insights into how IgG subclass and posttranslational modifications influence antibody activity and discusses their implications in designing therapeutic antibodies for different clinical indications.
Review
Immunology
Silvia Redondo-Garcia, Christopher Barritt, Charys Papagregoriou, Muchaala Yeboah, Bjorn Frendeus, Mark S. Cragg, Ali Roghanian
Summary: Human leukocyte immunoglobulin-like receptors (LILRs) are an important family of immunomodulatory receptors associated with various pathologies. These receptors play a crucial role in immune activation and inhibition, making them potential targets for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Oncology
Linda Martensson, Robert Oldham, Marie Borggren, Mathilda Kovacek, Therese Blidberg, Ulla-Carin Tornberg, Ingrid Karlsson, Steve Beers, Mark Cragg, Ingrid Teige, Bjorn Frendeus
Meeting Abstract
Oncology
Linda Martensson, Kirsty Cleary, Petra Holmkvist, Mathilda Kovacek, Carolin Svensson, Monika Semmrich, Therese Blidberg, Mimoza Demiri, Osman Dadas, Marie Borggren, Vici Pitic, Sean H. Lim, Stephen A. Beers, Susanne Gertsson, Kristoffer S. Rohrberg, Ingrid Karlsson, Andres McAllister, Mark S. Cragg, Bjorn Frendeus, Ingrid Teige
Meeting Abstract
Oncology
Marcus A. Widdess, H. T. Claude Chan, Christine A. Penfold C. Ian Mockridge, Tatyana Inzhelevskaya, Hannah J. Metcalfe, Mark S. Cragg, Aymen Al-Shamkhani
CANCER IMMUNOLOGY RESEARCH
(2022)