Article
Medicine, General & Internal
Kristy Nguyen, Pierre Juillard, Simon Hawke, Georges E. Grau, Felix Marsh-Wakefield
Summary: The breakdown of the blood-brain barrier and the migration of lymphocytes play important roles in the development of multiple sclerosis. Treatment with alemtuzumab can inhibit inflammation in the central nervous system, but its effect on T cell migration needs more study.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Carla Rodriguez-Mogeda, Sabela Rodriguez-Lorenzo, Jiji Attia, Jack van Horssen, Maarten E. Witte, Helga E. de Vries
Summary: Multiple sclerosis is an inflammatory disease where B cells play a crucial role in the pathogenesis, migrating into the central nervous system through various routes. Understanding the routes of B cell entry into the inflamed CNS is essential for comprehending the disease.
Review
Neurosciences
Gabriele Angelini, Alessandro Bani, Gabriela Constantin, Barbara Rossi
Summary: The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) are two complex structures that protect the central nervous system (CNS) from harmful agents and immune cells. During neuroinflammatory disorders like multiple sclerosis (MS), the BBB and BCSFB undergo changes that allow immune cells to enter the CNS and contribute to the disease. T helper (Th) lymphocytes, specifically Th1 and Th17 cells, play a key role in the pathogenesis of MS and interact with CNS barriers, leading to barrier dysfunction. This review discusses the molecular basis of the interactions between Th cells and CNS barriers and explores the role of the dura mater and arachnoid layer in CNS inflammatory diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Sebok K. Halder, Richard Milner
Summary: Fifty years of research on multiple sclerosis have provided significant insights into this neurological disease, revealing its characteristics and raising questions about the initial trigger of the inflammatory demyelinating process. Recent studies suggest that hypoxia, in addition to the immune system, may play a role in disease progression, leading researchers to investigate the impact of manipulating inspired oxygen levels.
Article
Clinical Neurology
Sebok K. Halder, Richard Milner
Summary: Multiple sclerosis is an autoimmune disease that may be affected by hypoxia as a new potential trigger for the inflammatory demyelinating process. Studies have shown the presence of hypoxia in early demyelinating lesions, prompting researchers to investigate how oxygen levels impact disease progression.
Article
Cell Biology
Mariana Castro Dias, Adolfo Odriozola Quesada, Sasha Soldati, Fabio Bosch, Isabelle Gruber, Tobias Hildbrand, Derya Sonmez, Tejas Khire, Guillaume Witz, James L. McGrath, Joerg Piontek, Masuo Kondoh, Urban Deutsch, Benoit Zuber, Britta Engelhardt
Summary: The study suggests that tricellular junctions of the BBB serve as novel sites for T cell diapedesis, different from the previously believed cellular junctions. By manipulating the expression of tricellular junctional proteins or targeting chemokines, the ability of T cells to cross the BBB can be enhanced or suppressed.
JOURNAL OF CELL SCIENCE
(2021)
Article
Immunology
Luca Marchetti, David Francisco, Sasha Soldati, Neda Haghayegh Jahromi, Sara Barcos, Isabelle Gruber, Javier R. Pareja, Aude Thiriot, Ulrich von Andrian, Urban Deutsch, Ruth Lyck, Remy Bruggmann, Britta Engelhardt
Summary: The migration of CD4(+) effector/memory T cells across the blood-brain barrier (BBB) is a critical step in multiple sclerosis (MS) or its animal model, EAE. Researchers identified Ackr1 as one of the main candidate genes upregulated in pMBMECs favoring transcellular T-cell diapedesis. Additionally, endothelial ACKR1 plays a role in shuttling chemokines across the BBB during EAE pathogenesis, enhancing transcellular T-cell diapedesis during autoimmune neuroinflammation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Review
Chemistry, Medicinal
Lukasz Kalkowski, Piotr Walczak, Marcin P. P. Mycko, Izabela Malysz-Cymborska
Summary: Multiple sclerosis is a chronic demyelinating disease, and current FDA-approved disease-modifying therapeutics can only alleviate the disease progression. Systemic drug administration may not be effective for therapeutic targets in the central nervous system. Therefore, alternative drug delivery strategies that improve drug accumulation in the brain should be considered for patients with rapidly progressing disease.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Thomas Gabriel Schreiner, Constantin Romanescu, Bogdan Ovidiu Popescu
Summary: This article reviews the role of the blood-brain barrier (BBB) in multiple sclerosis (MS) pathology, emphasizing the importance of neurovascular unit damage in MS onset and progression, as well as the impact of BBB cell alterations and immune cell penetration into the central nervous system on MS pathology.
Review
Biochemistry & Molecular Biology
Rodica Balasa, Laura Barcutean, Oana Mosora, Doina Manu
Summary: This review discusses the disruption of the blood-brain barrier (BBB) in multiple sclerosis (MS) pathogenesis, focusing on the impairment of the neurovascular unit (NVU) and metabolic and mitochondrial dysfunctions of BBB’s endothelial cells. It highlights the hypoxic hypothesis in MS, potential mechanisms of neurodegeneration in progressive forms of MS, and the possibility of BBB as a therapeutic target for delivering neuroprotective molecules into the central nervous system. Additionally, it explores the beneficial effects of disease-modifying therapies (DMTs) that can cross the BBB and act directly in the CNS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Ruoyu Li, Hui Li, Xiaoyan Yang, Huiru Hu, Peidong Liu, Hongbo Liu
Summary: This review summarizes the interaction and protective mechanisms between dendritic cells (DCs) and regulatory T cells (Tregs) in multiple sclerosis (MS), explores their potential value in the treatment of MS, and proposes new therapeutic directions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Joao Canto-Gomes, Carolina S. Silva, Rita Rb-Silva, Daniela Boleixa, Ana Martins da Silva, Remi Cheynier, Patricio Costa, Ines Gonzalez-Suarez, Margarida Correia-Neves, Joao J. Cerqueira, Claudia Nobrega
Summary: The aim of this study is to assess the peripheral immune system of newly diagnosed patients with relapsing remitting multiple sclerosis (RRMS) and identify immune features associated with clinical onset.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
S. M. Lunin, E. G. Novoselova, O. V. Glushkova, S. B. Parfenyuk, A. A. Kuzekova, T. V. Novoselova, M. G. Sharapov, E. K. Mubarakshina, R. G. Goncharov, M. O. Khrenov
Summary: This study showed that the immunomodulator thymulin and the antioxidant enzyme Prdx6 can improve the condition of blood-brain barrier (BBB) and alleviate symptoms of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Thymulin decreased immune cell activation, while Prdx6 reduced NOX1 and NOX4 gene expression in brain tissue, contributing to the improvements in BBB condition and health status. Simultaneous administration of thymulin and Prdx6 resulted in complete symptomatic restoration of mice with EAE.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Medicine, General & Internal
Rachel K. Ford, Pierre Juillard, Simon Hawke, Georges E. Grau, Felix Marsh-Wakefield
Summary: Cladribine treatment reduces trans-endothelial migration of T cell subsets in multiple sclerosis patients, contributing to disease control and maintenance of the integrity of the blood-brain barrier.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Mona Tarighi, Mehdi Shahbazi, Payam Saadat, Abdolreza Daraei, Ali Alizadeh Khatir, Kimiya Rahimifard, Mousa Mohammadnia-Afrouzi
Summary: This study examined the frequency and gene expression levels of regulatory T cells (Tregs) in secondary progressive multiple sclerosis (SPMS) patients. The results showed that the percentage of Tregs with CD4 and CD25 markers did not differ significantly compared to healthy controls, but the lymphocytes with CD4/CD25/FOXP3/Helios markers were significantly reduced in SPMS patients. The expression of the Helios gene was also decreased in these patients. These findings suggest that a deficiency in Tregs may be involved in the immunological mechanisms of SPMS.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Steven C. Koetzier, Rinze F. Neuteboom, Annet F. Wierenga-Wolf, Marie-Jose Melief, C. Louk de Mol, Angelique van Rijswijk, Willem A. Dik, Bieke Broux, Ronald van der Wal, Sjoerd A. A. van den Berg, Joost Smolders, Marvin M. van Luijn
Summary: This study found that effector memory proportions of Th cells were increased postpartum in MS patients without a postpartum relapse, with upregulation of CXCR3 on postpartum memory Th cells. However, this was not seen in relapsing patients. The pro-inflammatory state of memory Th cells during pregnancy may predict a postpartum relapse.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Allergy
Paulien Baeten, Lauren Van Zeebroeck, Markus Kleinewietfeld, Niels Hellings, Bieke Broux
Summary: Autoimmunity is caused by an unbalanced immune system, leading to various disorders. Patients with autoimmune diseases are commonly treated with broad-acting immunomodulatory drugs, but face risks of severe side effects. Regulatory T cells (Tregs) have the potential for cell therapy in autoimmune disorders, but require ex vivo manipulation to enhance their suppressive function.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Cindy Hoeks, Marjan Vanheusden, Liesbet M. Peeters, Piet Stinissen, Bieke Broux, Niels Hellings
Summary: Research found that CD4 CTL are resistant to suppression by Tregs in vitro, but the conditioned medium of CD4 CTL can accentuate the suppressive phenotype of Tregs. The CD4 CTL conditioned medium also skews memory TH cells towards a TH17 phenotype, and when cell-cell contact is established between CD4 CTL and TH cells, the proliferation of TH cells is no longer increased and Treg-mediated suppression is restored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Jan Spaas, Wouter M. A. Franssen, Charly Keytsman, Laura Blancquaert, Tim Vanmierlo, Jeroen Bogie, Bieke Broux, Niels Hellings, Jack van Horssen, Dheeraj Kumar Posa, David Hoetker, Shahid P. Baba, Wim Derave, Bert O. Eijnde
Summary: The study found that quenching of carbonyl (particularly acrolein) by carnosine may be a therapeutic strategy to counter inflammation and macromolecular damage in multiple sclerosis.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Celine Erens, Jana Van Broeckhoven, Cindy Hoeks, Gernot Schabbauer, Paul N. Cheng, Li Chen, Niels Hellings, Bieke Broux, Stefanie Lemmens, Sven Hendrix
Summary: L-arginine depletion holds promise as a therapeutic strategy after SCI, as it can improve functional recovery, reduce T-cell infiltration, suppress pro-inflammatory responses, decrease neuronal cell death, and decrease NO production.
Article
Cell Biology
Steven C. Koetzier, Jamie van Langelaar, Marie-Jose Melief, Annet F. Wierenga-Wolf, Cato E. A. Corsten, Katelijn M. Blok, Cindy Hoeks, Bieke Broux, Beatrijs Wokke, Marvin M. van Luijn, Joost Smolders
Summary: The effector programs of CD8(+) memory T cells in multiple sclerosis (MS) are influenced by transcription factors RUNX3, EOMES, and T-bet. This study found that the frequencies of RUNX3- and EOMES-expressing CD8(+) memory T cells were reduced in the blood of MS patients, but not in MS patients treated with natalizumab. CD8(+) memory T cells that co-express RUNX3 and EOMES and do not express T-bet were enriched in the MS cerebrospinal fluid and associated with brain residency-associated markers. These findings suggest that the co-expression of RUNX3 and EOMES defines CD8(+) memory T cells with a pre-existing brain residency-associated phenotype in MS.
Article
Clinical Neurology
Doryssa Hermans, Evelien Houben, Paulien Baeten, Helena Slaets, Kris Janssens, Cindy Hoeks, Baharak Hosseinkhani, Gayel Duran, Seppe Bormans, Elizabeth Gowing, Chloe Hoornaert, Lien Beckers, Wing Ka Fung, Horst Schroten, Hiroshi Ishikawa, Judith Fraussen, Ronald Thoelen, Helga E. de Vries, Gijs Kooij, Stephanie Zandee, Alexandre Prat, Niels Hellings, Bieke Broux
Summary: OSM plays an important role in neuro-inflammatory diseases, including MS, where it increases the responsiveness of lymphocytes and is produced by activated myeloid cells and astrocytes. In a preclinical model of MS, OSMR beta-deficient mice show milder symptoms, reduced Th17 cell infiltration, and BBB leakage. In vitro, OSM reduces BBB integrity, promotes CCL20 secretion by inflamed BBB-endothelial cells and astrocytes, and enhances Th17 cell adhesion.
ACTA NEUROPATHOLOGICA
(2022)
Review
Immunology
Negar Sadeghi Hassanabadi, Bieke Broux, Sonja Marinovic, Dagmar Gotthardt
Summary: Multiple sclerosis (MS) is a debilitating autoimmune disease with millions of patients worldwide. Recent studies have shown that innate lymphoid cells (ILCs), in addition to T cells, play a role in the disease pathology. However, the exact role of ILCs in MS is still controversial.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Cindy Hoeks, Gayel Duran, Niels Hellings, Bieke Broux
Summary: CD4 CTL, once considered an experimental artefact, are now recognized as a biologically relevant T cell subset with important functions in anti-viral, anti-tumor, and autoimmune responses. With the advancement of single cell analysis techniques, the study of CD4 CTL has been facilitated. This review summarizes the developmental path of CD4 CTL and presents markers for their detection and isolation. The subsets of CD4 CTL and their diverse functionalities are discussed.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Peripheral Vascular Disease
Doryssa Hermans, Carla Rodriguez-Mogeda, Hannelore Kemps, Annelies Bronckaers, E. de Vries Helga, Bieke Broux
Summary: Nectins and Necls proteins play crucial roles in vascular endothelium by supporting blood vessel formation, maintaining endothelial barrier, and guiding immune cell migration.
Article
Immunology
Melissa Schepers, Dean Paes, Assia Tiane, Ben Rombaut, Elisabeth Piccart, Lieve van Veggel, Pascal Gervois, Esther Wolfs, Ivo Lambrichts, Chiara Brullo, Olga Bruno, Ernesto Fedele, Roberta Ricciarelli, Charles Ffrench-Constant, Marie E. Bechler, Pauline van Schaik, Wia Baron, Evy Lefevere, Kobi Wasner, Anne Grunewald, Catherine Verfaillie, Paulien Baeten, Bieke Broux, Paul Wieringa, Niels Hellings, Jos Prickaerts, Tim Vanmierlo
Summary: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by central nervous system inflammation and demyelination. Current therapies are insufficient in halting or reversing disease progression. This study shows that selective inhibition of phosphodiesterase 4 (PDE4) promotes myelin repair and reduces inflammation. Inhibition of PDE4D enhances (re)myelination, while inhibition of PDE4B exerts anti-inflammatory effects. These findings suggest that gene specific PDE4 inhibitors could be potential therapeutic agents for MS.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Review
Biology
Doryssa Hermans, Lisa van Beers, Bieke Broux
Summary: Immune-cell activation is controlled by co-stimulatory or co-inhibitory signals provided by the cellular environment. The balance between activating and inhibitory receptors regulates immune homeostasis, and an imbalance can lead to chronic inflammation and autoimmunity. This review focuses on the expression pattern of Nectin binding partners as immune-activating and -inhibitory receptors and their role in health and autoimmunity.
Article
Immunology
Elien Grajchen, Melanie Loix, Paulien Baeten, Beatriz F. Corte-Real, Ibrahim Hamad, Sam Vanherle, Mansour Haidar, Jonas Dehairs, Jelle Y. Broos, James M. Ntambi, Robert Zimmermann, Rolf Breinbauer, Piet Stinissen, Niels Hellings, Sanne G. S. Verberk, Gijs Kooij, Martin Giera, Johannes V. Swinnen, Bieke Broux, Markus Kleinewietfeld, Jerome J. A. Hendriks, Jeroen F. J. Bogie
Summary: The imbalance between pathogenic and protective T cell subsets is a key feature of autoimmune disorders such as multiple sclerosis (MS). The molecular mechanisms underlying the impact of fatty acid metabolism on T cell physiology and autoimmunity are poorly understood. The study reveals that fatty acid desaturation by SCD1 acts as an endogenous brake on regulatory T-cell differentiation and enhances autoimmunity, suggesting potential therapeutic strategies for autoimmune disorders such as MS.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
