17 results on '"Gervois, Pascal"'
Search Results
2. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation
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Yshii, Lidia, Pasciuto, Emanuela, Bielefeld, Pascal, Mascali, Loriana, Lemaitre, Pierre, Marino, Marika, Dooley, James, Kouser, Lubna, Verschoren, Stijn, Lagou, Vasiliki, Kemps, Hannelore, Gervois, Pascal, de Boer, Antina, Burton, Oliver T., Wahis, Jérôme, Verhaert, Jens, Tareen, Samar H. K., Roca, Carlos P., Singh, Kailash, Whyte, Carly E., Kerstens, Axelle, Callaerts-Vegh, Zsuzsanna, Poovathingal, Suresh, Prezzemolo, Teresa, Wierda, Keimpe, Dashwood, Amy, Xie, Junhua, Van Wonterghem, Elien, Creemers, Eline, Aloulou, Meryem, Gsell, Willy, Abiega, Oihane, Munck, Sebastian, Vandenbroucke, Roosmarijn E., Bronckaers, Annelies, Lemmens, Robin, De Strooper, Bart, Van Den Bosch, Ludo, Himmelreich, Uwe, Fitzsimons, Carlos P., Holt, Matthew G., and Liston, Adrian
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- 2022
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3. The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris
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Vanherle, Sam, Jorissen, Winde, Dierckx, Tess, Loix, Melanie, Grajchen, Elien, Mingneau, Fleur, Guns, Jeroen, Gervois, Pascal, Lambrichts, Ivo, Dehairs, Jonas, Swinnen, Johannes V., Mulder, Monique T., Remaley, Alan T., Haidar, Mansour, Hendriks, Jerome J.A., and Bogie, Jeroen J.F.
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- 2022
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4. Optimization of whole slide imaging scan settings for computer vision using human lung cancer tissue.
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Geubbelmans, Melvin, Claes, Jari, Nijsten, Kim, Gervois, Pascal, Appeltans, Simon, Martens, Sandrina, Wolfs, Esther, Thomeer, Michiel, Valkenborg, Dirk, and Faes, Christel
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SPATIAL analysis (Statistics) ,HEMATOXYLIN & eosin staining ,COMPUTER vision ,ARTIFICIAL intelligence ,LUNG cancer - Abstract
Digital pathology has become increasingly popular for research and clinical applications. Using high-quality microscopes to produce Whole Slide Images of tumor tissue enables the discovery of insights into biological aspects invisible to the human eye. These are acquired through downstream analyses using spatial statistics and artificial intelligence. Determination of the quality and consistency of these images is needed to ensure accurate outcomes when identifying clinical and subclinical image features. Additionally, the time-intensive process of generating high-volume images results in a trade-off that needs to be carefully balanced. This study aims to determine optimal instrument settings to generate representative images of pathological tissue using digital microscopy. Using various settings, an H&E stained sample was scanned using the ZEISS Axio Scan.Z1. Next, nucleus segmentation was performed on resulting images using StarDist. Subsequently, detections were compared between scans using a matching algorithm. Finally, nucleus-level information was compared between scans. Results indicated that while general matching percentages were high, similarity between information from replicates was relatively low. Additionally, settings resulting in longer scanning times and increased data volume did not increase similarity between replicates. In conclusion, the scan setting ultimately deemed optimal combined consistent and qualitative performance with low throughput time. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Differential Expression of Fibroblast Activation Protein-Alpha and Lysyl Oxidase in Subtypes of Ameloblastoma
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Vangansewinkel, Tim, primary, Driesen, Ronald, additional, Agbaje, Jimoh Olubanwo, additional, Gervois, Pascal, additional, Olumuyiwa Adisa, Akinyele, additional, Olusanya, Adeola Adenike, additional, Arotiba, Juwon Tunde, additional, Wolfs, Esther, additional, Lambrichts, Ivo, additional, and Politis, Constantinus, additional
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- 2024
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6. The Effect of Leukocyte- and Platelet-Rich Fibrin on Central and Peripheral Nervous System Neurons—Implications for Biomaterial Applicability
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Lambrichts, Ivo, primary, Wolfs, Esther, additional, Bronckaers, Annelies, additional, Gervois, Pascal, additional, and Vangansewinkel, Tim, additional
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- 2023
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7. Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination
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Garcia Corrales, Aida V., primary, Verberk, Sanne G. S., additional, Haidar, Mansour, additional, Grajchen, Elien, additional, Dehairs, Jonas, additional, Vanherle, Sam, additional, Loix, Melanie, additional, Weytjens, Tine, additional, Gervois, Pascal, additional, Matsuzaka, Takashi, additional, Lambrichts, Ivo, additional, Swinnen, Johannes V., additional, Bogie, Jeroen F. J., additional, and Hendriks, Jerome J. A., additional
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- 2023
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8. Differential expression of fibroblast activation protein-alpha and lysyl oxidase in subtypes of ameloblastoma
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Vangansewinkel, Tim, primary, Driesen, Ronald, additional, Olubanwo Agbaje, Jimoh, additional, Gervois, Pascal, additional, Olumuyiwa Adisa, Akinyele, additional, Adenike Olusanya, Adeola, additional, Tunde Arotiba, Juwon, additional, Wolfs, Esther, additional, Lambrichts, Ivo, additional, and Politis, Constantinus, additional
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- 2023
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9. Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination.
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Corrales, Aida V. Garcia, Verberk, Sanne G. S., Haidar, Mansour, Grajchen, Elien, Dehairs, Jonas, Vanherle, Sam, Loix, Melanie, Weytjens, Tine, Gervois, Pascal, Takashi Matsuzaka, Lambrichts, Ivo, Swinnen, Johannes V., Bogie, Jeroen F. J., and Hendriks, Jerome J. A.
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FOAM cells ,FATTY acids ,MONOUNSATURATED fatty acids ,UNSATURATED fatty acids ,REMANUFACTURING ,DEMYELINATION - Abstract
A hallmark of multiple sclerosis (MS) is the formation of multiple focal demyelinating lesions within the central nervous system (CNS). These lesions mainly consist of phagocytes that play a key role in lesion progression and remyelination, and therefore represent a promising therapeutic target in MS. We recently showed that unsaturated fatty acids produced by stearoyl-CoA desaturase-1 induce inflammatory foam cell formation during demyelination. These fatty acids are elongated by the "elongation of very long chain fatty acids" proteins (ELOVLs), generating a series of functionally distinct lipids. Here, we show that the expression and activity of ELOVLs are altered in myelin-induced foam cells. Especially ELOVL6, an enzyme responsible for converting saturated and monounsaturated C16 fatty acids into C18 species, was found to be up-regulated in myelin phagocytosing phagocytes in vitro and in MS lesions. Depletion of Elovl6 induced a repair-promoting phagocyte phenotype through activation of the S1P/PPAR? pathway. Elovl6-deficient foamy macrophages showed enhanced ABCA1-mediated lipid efflux, increased production of neurotrophic factors, and reduced expression of inflammatory mediators. Moreover, our data show that ELOVL6 hampers CNS repair, as Elovl6 deficiency prevented demyelination and boosted remyelination in organotypic brain slice cultures and the mouse cuprizone model. These findings indicate that targeting ELOVL6 activity may be an effective strategy to stimulate CNS repair in MS and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation
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Dierckx, Tess, primary, Vanherle, Sam, additional, Haidar, Mansour, additional, Grajchen, Elien, additional, Mingneau, Fleur, additional, Gervois, Pascal, additional, Wolfs, Esther, additional, Bylemans, Dany, additional, Voet, Arnout, additional, Nguyen, Tien, additional, Hamad, Ibrahim, additional, Kleinewietfeld, Markus, additional, Bogie, Jeroen F. J., additional, and Hendriks, Jerome J. A., additional
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- 2022
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11. Non-invasive brain stimulation as therapeutic approach for ischemic stroke: Insights into the (sub)cellular mechanisms
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Kemps, Hannelore, primary, Gervois, Pascal, additional, Brône, Bert, additional, Lemmens, Robin, additional, and Bronckaers, Annelies, additional
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- 2022
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12. Targeting lipophagy in macrophages improves repair in multiple sclerosis
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Haidar, Mansour, primary, Loix, Melanie, additional, Vanherle, Sam, additional, Dierckx, Tess, additional, Vangansewinkel, Tim, additional, Gervois, Pascal, additional, Wolfs, Esther, additional, Lambrichts, Ivo, additional, Bogie, Jeroen F.J., additional, and Hendriks, Jerome J.A., additional
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- 2022
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13. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation
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Yshii, Lidia, primary, Pasciuto, Emanuela, additional, Bielefeld, Pascal, additional, Mascali, Loriana, additional, Lemaitre, Pierre, additional, Marino, Marika, additional, Dooley, James, additional, Kouser, Lubna, additional, Verschoren, Stijn, additional, Lagou, Vasiliki, additional, Kemps, Hannelore, additional, Gervois, Pascal, additional, de Boer, Antina, additional, Burton, Oliver T., additional, Wahis, Jérôme, additional, Verhaert, Jens, additional, Tareen, Samar, additional, Roca, Carlos P., additional, Singh, Kailash, additional, Whyte, Carly E., additional, Kerstens, Axelle, additional, Callaerts-Vegh, Zsuzsanna, additional, Poovathingal, Suresh, additional, Prezzemolo, Teresa, additional, Wierda, Keimpe, additional, Dashwood, Amy, additional, Xie, Junhua, additional, Van Wonterghem, Elien, additional, Creemers, Eline, additional, Aloulou, Meryem, additional, Gsell, Willy, additional, Abiega, Oihane, additional, Munck, Sebastian, additional, Vandenbroucke, Roosmarijn E., additional, Bronckaers, Annelies, additional, Lemmens, Robin, additional, De Strooper, Bart, additional, Van Den Bosch, Ludo, additional, Himmelreich, Uwe, additional, Fitzsimons, Carlos P., additional, Holt, Matthew G., additional, and Liston, Adrian, additional
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- 2022
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14. Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin damaging hallmarks of multiple sclerosis
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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 Grünewald, Catherine Verfaillie, Paulien Baeten, Bieke Broux, Paul Wieringa, Niels Hellings, Jos Prickaerts, Tim Vanmierlo, Grunewald, Anne/0000-0002-4179-2994, SCHEPERS, Melissa, PAES, Dean, TIANE, Assia, ROMBAUT, Ben, PICCART, Elisabeth, VAN VEGGEL, Lieve, GERVOIS, Pascal, Brullo, Chiara, Bruno, Olga, Fedele, Ernesto, Ricciarelli, Roberta, Ffrench-Constant, Charles, Bechler, Marie E., Schaik, Pauline van, WOLFS, Esther, LAMBRICHTS, Ivo, Baron, Wia, LEFEVERE, Evy, Wasner, Kobi, Gruenewald, Anne, Verfaillie, Catherine, Wieringa, Paul, Prickaerts, Jos, BROUX, Bieke, BAETEN, Paulien, HELLINGS, Niels, VANMIERLO, Tim, RS: MHeNs - R3 - Neuroscience, Basic Neuroscience 2, Basic Neuroscience 1, CTR, RS: MERLN - Complex Tissue Regeneration (CTR), and Psychiatrie & Neuropsychologie
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Multiple sclerosis ,Behavioral Neuroscience ,Neuroinflammation ,Remyelination ,Endocrine and Autonomic Systems ,Phosphodiesterases ,Immunology ,Biochemistry, biophysics & molecular biology [F05] [Life sciences] ,Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant] - Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by focal inflammatory lesions and prominent demyelination. Even though the currently available therapies are effective in treating the initial stages of disease, they are unable to halt or reverse disease progression into the chronic progressive stage. Thus far, no repair-inducing treatments are available for progressive MS patients. Hence, there is an urgent need for the development of new therapeutic strategies either targeting the destructive immunological demyelination or boosting endogenous repair mechanisms. Using in vitro, ex vivo, and in vivo models, we demonstrate that selective inhibition of phosphodiesterase 4 (PDE4), a family of enzymes that hydrolyzes and inactivates cyclic adenosine monophosphate (cAMP), reduces inflammation and promotes myelin repair. More specifically, we segregated the myelination-promoting and anti-inflammatory effects into a PDE4Dand PDE4B-dependent process respectively. We show that inhibition of PDE4D boosts oligodendrocyte progenitor cells (OPC) differentiation and enhances (re)myelination of both murine OPCs and human iPSC-derived OPCs. In addition, PDE4D inhibition promotes in vivo remyelination in the cuprizone model, which is accompanied by improved spatial memory and reduced visual evoked potential latency times. We further identified that PDE4B-specific inhibition exerts anti-inflammatory effects since it lowers in vitro monocytic nitric oxide (NO) production and improves in vivo neurological scores during the early phase of experimental autoimmune encephalomyelitis (EAE). In contrast to the pan PDE4 inhibitor roflumilast, the therapeutic dose of both the PDE4B-specific inhibitor A33 and the PDE4D-specific inhibitor Gebr32a did not trigger emesis-like side effects in rodents. Finally, we report distinct PDE4D isoform expression patterns in human area postrema neurons and human oligodendroglia lineage cells. Using the CRISPR-Cas9 system, we confirmed that pde4d1/2 and pde4d6 are the key targets to induce OPC differentiation. Collectively, these data demonstrate that gene specific PDE4 inhibitors have potential as novel therapeutic agents for targeting the distinct disease processes of MS. This work has been supported by FWO (12G0817N, 1S57521N, G041421N, and 12G0817N), Fondation Charctot Stichting (ID2020- 0019), Nationale Belgische Multiple Sclerose Liga (Charco18VT), MS Liga Vlaanderen and Stichting MS Research (18-1016 MS). MS, EP, JP and TV have a proprietary interest in selective PDE4D inhibitors for the treatment of demyelinating disorders and neurodegenerative disorders. JP has a proprietary interest in the PDE4 inhibitor roflumilast for the treatment of cognitive impairment as well as PDE4D inhibitors for the treatment of Alzheimer’s disease. We thank Prof. Dr. O.N. Viacheslav (University Medical Center Hamburg-Eppendorf, German Center for Cardiovascular Research) and Prof. Dr. M. Conti (University of California), for providing the PDE4B KO animals. Furthermore, we thank Rewind Therapeutics for providing the visual evoked potential equipment.
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- 2023
15. Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation
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Tess Dierckx, Sam Vanherle, Mansour Haidar, Elien Grajchen, Fleur Mingneau, Pascal Gervois, Esther Wolfs, Dany Bylemans, Arnout Voet, Tien Nguyen, Ibrahim Hamad, Markus Kleinewietfeld, Jeroen F. J. Bogie, Jerome J. A. Hendriks, voet, arnout/0000-0002-3329-2703, Wolfs, Esther/0000-0001-9277-6524, Kleinewietfeld, Markus/0000-0002-2832-3149, Gervois, Pascal/0000-0002-8320-1320, Hendriks, Jerome/0000-0002-7717-8582, DIERCKX, Tess, VANHERLE, Sam, HAIDAR, Mansour, GRAJCHEN, Elien, MINGNEAU, Fleur, GERVOIS, Pascal, WOLFS, Esther, Bylemans, Dany, Voet, Arnout, Nguyen , Tien, HAMAD, Ibrahim, KLEINEWIETFELD, Markus, BOGIE, Jeroen, and HENDRIKS, Jerome
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Oligodendrocyte Precursor Cells ,Mice, Inbred C57BL ,Mice ,Oligodendroglia ,Multidisciplinary ,Remyelination ,Phloretin ,Animals ,Cell Differentiation ,multiple sclerosis ,oligodendrocyte ,Myelin Sheath - Abstract
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells. Previously, we found that phloretin, a flavonoid abundantly present in apples and strawberries, reduces neuroinflammation by driving macrophages toward an antiinflammatory phenotype. Here, we show that phloretin also markedly stimulates remyelination in ex vivo and in vivo animal models. Improved remyelination was attributed to a direct impact of phloretin on OPC maturation and occurred independently from alterations in microglia function and inflammation. We found, mechanistically, that phloretin acts as a direct ligand for the fatty acid sensing nuclear receptor peroxisome proliferator-activated receptor gamma, thereby promoting the maturation of OPCs. Together, our findings indicate that phloretin has proregenerative properties in central nervous system disorders, with potentially broad implications for the development of therapeutic strategies and dietary interventions aimed at promoting remyelination. This work was supported by the Flemish Fund for Scientific Research (FWO Vlaanderen; G099618, 12J9119N, and 1501720N). M.K. was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program (640116), by a Salk grant from the government of Flanders, Belgium, and by the FWO (G0G1216N and G080121N)
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- 2022
16. Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological neuroinflammation
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Lidia Yshii, Emanuela Pasciuto, Pascal Bielefeld, Loriana Mascali, Pierre Lemaitre, Marika Marino, James Dooley, Lubna Kouser, Stijn Verschoren, Vasiliki Lagou, Hannelore Kemps, Pascal Gervois, Antina de Boer, Oliver T. Burton, Jérôme Wahis, Jens Verhaert, Samar H. K. Tareen, Carlos P. Roca, Kailash Singh, Carly E. Whyte, Axelle Kerstens, Zsuzsanna Callaerts-Vegh, Suresh Poovathingal, Teresa Prezzemolo, Keimpe Wierda, Amy Dashwood, Junhua Xie, Elien Van Wonterghem, Eline Creemers, Meryem Aloulou, Willy Gsell, Oihane Abiega, Sebastian Munck, Roosmarijn E. Vandenbroucke, Annelies Bronckaers, Robin Lemmens, Bart De Strooper, Ludo Van Den Bosch, Uwe Himmelreich, Carlos P. Fitzsimons, Matthew G. Holt, Adrian Liston, Pasciuto, Emanuela [0000-0002-5391-9585], Marino, Marika [0000-0001-6773-6176], Dooley, James [0000-0003-3154-4708], Verschoren, Stijn [0000-0001-6733-3481], Kemps, Hannelore [0000-0001-9248-1697], Gervois, Pascal [0000-0002-8320-1320], Burton, Oliver T [0000-0003-3884-7373], Singh, Kailash [0000-0002-6771-7757], Whyte, Carly E [0000-0001-6556-6855], Callaerts-Vegh, Zsuzsanna [0000-0001-9091-2078], Dashwood, Amy [0000-0002-4340-377X], Gsell, Willy [0000-0001-7334-6107], Vandenbroucke, Roosmarijn E [0000-0002-8327-620X], Liston, Adrian [0000-0002-6272-4085], Apollo - University of Cambridge Repository, Benson-Rumiz, Alicia, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Amsterdam [Amsterdam] (UvA), The Babraham Institute [Cambridge, UK], Brunel University London [Uxbridge], Hasselt University (UHasselt), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), VIB [Belgium], VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), Universiteit Gent = Ghent University (UGENT), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Hospitals Leuven [Leuven], University College of London [London] (UCL), Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Pasciuto, Emanuela/0000-0002-5391-9585, Aloulou, Meryem/0000-0003-4590-230X, Dooley, James/0000-0003-3154-4708, Verschoren, Stijn/0000-0001-6733-3481, Kemps, Hannelore/0000-0001-9248-1697, Marino, Marika/0000-0001-6773-6176, Lemaitre, Pierre/0000-0003-0687-8685, Structural and Functional Plasticity of the nervous system (SILS, FNWI), SILS Other Research (FNWI), and Instituto de Investigação e Inovação em Saúde
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EXPRESSION ,Immunology ,Neuroimmunology ,631/250/127/1213 ,THERAPY ,T-Lymphocytes, Regulatory ,MICROGLIA ,Mice ,Medicine and Health Sciences ,Immunology and Allergy ,Animals ,Humans ,Interleukin-2 / genetics ,REPAIR ,Biological Products ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Interleukins ,article ,Biology and Life Sciences ,631/250/371 ,Brain ,631/250/251 ,REG-CELLS ,Regulatory T cells ,Astrocytes ,631/250/1619/554/1898/1271 ,Neuroinflammatory Diseases ,Interleukin-2 ,Immunotherapy ,SYSTEM ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,PACKAGE - Abstract
The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification of both effective targets for local immune modulation and a delivery system capable of crossing the blood-brain barrier. The recent identification and characterization of a small population of regulatory T (Treg) cells resident in the brain presents one such potential therapeutic target. Here, we identified brain interleukin 2 (IL-2) levels as a limiting factor for brain-resident Treg cells. We developed a gene-delivery approach for astrocytes, with a small-molecule on-switch to allow temporal control, and enhanced production in reactive astrocytes to spatially direct delivery to inflammatory sites. Mice with brain-specific IL-2 delivery were protected in traumatic brain injury, stroke and multiple sclerosis models, without impacting the peripheral immune system. These results validate brain-specific IL-2 gene delivery as effective protection against neuroinflammation, and provide a versatile platform for delivery of diverse biologics to neuroinflammatory patients. The work was supported by the VIB, an ERC Consolidator Grant TissueTreg (to A.L.), an ERC Proof of Concept Grant TreatBrainDamage (to A.L.), an ERC Starting Grant AstroFunc (to M.G.H.), an ERC Proof of Concept Grant AD-VIP (to M.G.H.), FWO Research Grant 1513616N (to M.G.H.), Thierry Latran Foundation Grant SOD-VIP (to M.G.H.), an ERNAET Chair (H2020-WIDESPREAD-2018-2020-6; NCBio: 951923; to M.G.H.), FWO Research Grants 1503420N (to E.P.) and 1513020N (to J.W.), an SAO-FRA pilot grant (20190032, to E.P.), and the Biotechnology and Biological Sciences Research Council through Institute Strategic Program Grant funding BBS/E/B/000C0427 and BBS/E/B/000C0428, and the Biotechnology and Biological Sciences Research Council Core Capability Grant to the Babraham Institute. E.P., V.L., M.M., P.G., J.W. and A.d.B. were supported by fellowships from the FWO. R.L. is a senior clinical investigator of FWO Flanders. P.B., O.A. and C.P.F. were supported by an ERA-NET-NEURON grant EJTC 2016 to C.P.F. and by the Netherlands Organization for Scientific research (NWO). The authors acknowledge the important contributions of J. Haughton (VIB) for mouse husbandry, M. Rincon (VIB) for advice on AAV design and production, K. Vennekens for technical support, P. -A. Penttila and the KUL FACS Core, J. Wouters and the KUL Molecular Small Animal Imaging Center (MoSAIC), S. Walker and the Babraham Institute Imaging Core, the VIB Bio-Imaging Core, the VIB Single Cell Sequencing Core, and R. Breedijk, M. Hink and the Leeuwenhoek Center for Advanced Microscopy at the University of Amsterdam.
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- 2022
17. The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris
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Sam Vanherle, Winde Jorissen, Tess Dierckx, Melanie Loix, Elien Grajchen, Fleur Mingneau, Jeroen Guns, Pascal Gervois, Ivo Lambrichts, Jonas Dehairs, Johannes V. Swinnen, Monique T. Mulder, Alan T. Remaley, Mansour Haidar, Jerome J.A. Hendriks, Jeroen J.F. Bogie, Guns, Jeroen/0000-0003-0464-2601, VANHERLE, Sam, JORISSEN, Winde, DIERCKX, Tess, LOIX, Melanie, GRAJCHEN, Elien, MINGNEAU, Fleur, GUNS, Jeroen, GERVOIS, Pascal, LAMBRICHTS, Ivo, Dehairs, Jonas, Swinnen, Johannes, V, Mulder, Monique T., Remaley, Alan T., HAIDAR, Mansour, HENDRIKS, Jerome, BOGIE, Jeroen, and Internal Medicine
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Apolipoprotein A-I ,Neuroscience [CP] ,phagocyte ,lipid droplet degradation ,myelin debris clearance ,General Biochemistry, Genetics and Molecular Biology ,remyelination ,Remyelination ,ApoA-I mimetic peptide 5A ,Humans ,Peptides ,Myelin Sheath ,Demyelinating Diseases - Abstract
The progressive nature of demyelinating diseases lies in the inability of the central nervous system (CNS) to induce proper remyelination. Recently, we and others demonstrated that a dysregulated innate immune response partially underlies failure of CNS remyelination. Extensive accumulation of myelin-derived lipids and an inability to process these lipids was found to induce a disease-promoting phagocyte phenotype. Hence, restoring the ability of these phagocytes to metabolize and efflux myelin-derived lipids represents a promising strategy to promote remyelination. Here, we show that ApoA-I mimetic peptide 5A, a molecule well known to promote activity of the lipid efflux transporter ABCA1, markedly enhances remyelination. Mechanistically, we find that the repair-inducing properties of 5A are attributable to increased clearance and metabolism of remyelination-inhibiting myelin debris via the fatty acid translocase protein CD36, which is transcriptionally controlled by the ABCA1-JAK2-STAT3 signaling pathway. Altogether, our findings indi-cate that 5A promotes remyelination by stimulating clearance and degradation of myelin debris. We thank M.P. Tulleners for excellent technical assistance. The work was financially supported by the Research Foundation of Flanders (FWO Vlaanderen; 1S15519N, G099618FWO, and 12J9119N) and the Interreg V-A EMR program (EURLIPIDS, EMR23). The funding agencies had no role in the design, analysis, or writing of the article.
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- 2022
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