45 results on '"Dierckx T"'
Search Results
2. The influence of thyroid state on hypothalamic AMP-activated protein kinase pathways in broilers
- Author
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Lamberigts, C., primary, Wang, Y., additional, Dierckx, T., additional, Buys, N., additional, Everaert, N., additional, and Buyse, J., additional
- Published
- 2021
- Full Text
- View/download PDF
3. Peer Review #2 of "Predictive values of stool-based tests for mucosal healing among Taiwanese patients with ulcerative colitis: a retrospective cohort analysis (v0.1)"
- Author
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Dierckx, T, additional
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- 2020
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4. Quantifying chronic inflammatory burden from transcriptomes in viral and immune-mediated pathologies : Het kwantificeren van chronische ontstekingslast vanuit transcriptomen in virale en immuungemedieerde pathologieën
- Author
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Dierckx, T, Van Weyenbergh, J, Vrancken, B, and Vandamme, A-M
- Abstract
Human T-Cell Leukemia Virus Type 1, HTLV-1, is a pathogenic retrovirus infecting approximately 10 million individuals worldwide. The virus causes two distinct pathologies: Adult T-cell leukemia/lymphoma (ATL) and HTLV-1 Associated Myelopathy / Tropical Spastic Paraparesis (HAM/TSP). The common treatment of ATL currently consists of combination therapy with interferon (IFN) α and zidovudine. However, early reports showed IFN-β was also an effective treatment strategy, though IFN-α treatment became the standard based on empirical results. To explore the potential viability of IFN-β treatment in ATL, we tested the differential effects of IFN-α and -β on short term PBMC cultures of ATL patients and concluded that IFN‑β has superior anti‑proliferative and pro‑apoptotic effects. Additional meta‑analysis in four ATL gene expression datasets revealed a consistent decrease in RORC transcript abundance. In addition, a robust negative correlation exists between IL17C gene expression and proliferative gene expression in ATL and in other lymphoid leukemias. The transcriptomic experiments used in these studies also showed that inflammation could serve a protective role in ATL. As HTLV-1's other major pathology, HAM/TSP, is a neuroinflammatory disorder, we aimed to find a robust way of quantifying the inflammatory burden in transcriptomic experiments. Glycoprotein Acetylation (GlycA) is a novel biomarker for inflammation quantified in blood serum or plasma using Nuclear Magnetic Resonance (NMR) spectroscopy. This marker is a summary measure associated with a broad range of inflammatory processes and can be interpreted as a patient's chronic inflammatory burden. Using various machine learning algorithms on a large collection of paired NMR measurements and blood gene expression profiles, we constructed a predictive model which quantifies relative GlycA concentration from the gene transcript abundance in a patient's blood. This predictive model was first shown to replicate published GlycA associations. Then, novel predictions were made using publicly available third‑party data, which were tested, and confirmed to be accurate, using new NMR experiments. The GlycA measurements in Inflammatory Bowel Disease (IBD) and Systemic Lupus Erythematosus (SLE) were studied in greater detail. In IBD, GlycA concentration in patient serum samples was found to be higher than what was measured in healthy controls. In patients that responded to treatment and achieved mucosal healing, GlycA fell back down to the levels observed in healthy controls. Patients that showed an endoscopic treatment response but did not achieve full mucosal healing showed a GlycA decrease but fell short of returning to the healthy control GlycA levels. Considering our data shows that GlycA tracks disease activity even in patients without elevated C-reactive protein, our results demonstrate that GlycA holds great promise as a serological biomarker for disease activity in IBD. In SLE, our results show that GlycA levels are higher in SLE patients than those observed in healthy controls and even in nephritic controls without lupus, despite the altered renal function of the latter. We find that GlycA is associated to the SLE disease activity index and that proliferative lupus nephritis patients have higher GlycA concentrations than non‑proliferative patients at time of renal biopsy. When comparing performance of GlycA to traditional biomarkers, we show that GlycA is the more informative biomarker. (IWT project 141614: A transcriptomic approach to determine immunomodulatory therapeutic strategies in current and novel viral epidemics) status: published
- Published
- 2019
5. Co-crystal structure of NAMPT dimer with KPT-9274
- Author
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Neggers, J.E., primary, Kwanten, B., additional, Dierckx, T., additional, Noguchi, H., additional, Voet, A., additional, Vercruysse, T., additional, Baloglu, E., additional, Senapedis, W., additional, Jacquemyn, M., additional, and Daelemans, D., additional
- Published
- 2018
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6. IFN-β induces greater antiproliferative and proapoptotic effects and increased p53 signaling compared with IFN-α in PBMCs of Adult T-cell Leukemia/Lymphoma patients
- Author
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Dierckx, T, primary, Khouri, R, additional, Menezes, S M, additional, Decanine, D, additional, Farre, L, additional, Bittencourt, A, additional, Vandamme, A M, additional, and Van Weyenbergh, J, additional
- Published
- 2017
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7. Cryptic diversity within species or different species? A taxonomical question studied using the Praomys and Hylomyscus Rodentia genera of the Kisangani region (D.R.Congo) as an example
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Kennis, J., Nicolas, V., Katuala, P. G. B., Wendelen, W., Huselmans, J., Verheyen, E., van Houtte, N., Dierckx, T., Dudu, A. M., and Leirs, Herwig
- Published
- 2007
8. The characterization of the Kilimanjaro Lophuromys aquilus True 1892 population and the description of five new Lophuromys species (Rodentia, Muridae)
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Walter Verheyen, Jan Hulselmans, Dierckx, T., Mulungu, L. S., Herwig Leirs, Corti, M., and ERIK VERHEYEN
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- 2007
9. Craniometric, cytogenetic and genetic characterization of the Kilimanjaro Lophuromys aquilus True 1892 population, its implications for the taxonomy of the L. flavopunctatus species complex and the description of five new taxa (Rodentia: Muridae)
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Verheyen, W., Huselmans, J., Dierckx, T., Mulungu, L., Verheyen, E., Corti, M., Peterhans Kerbis, J., and Leirs, Herwig
- Published
- 2007
10. A craniometric and genetic approach to the systematics of the genus Dasymys PETERS, 1875 and the description of three new taxa (Rodentia, Muridae, Africa)
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Walter Verheyen, Jan Hulselmans, Dierckx, T., Colyn, M., Herwig Leirs, ERIK VERHEYEN, Department of Biology - Antwerp (UA), University of Antwerp (UA), Evolutionary Ecology Group, Universiteit Antwerpen, Universiteit Antwerpen = University of Antwerpen [Antwerpen], Ethologie, éVolution, Ecologie (EVE), Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Danish Pest Infestation Laboratory, Faculty of Agricultural Sciences, Department of Integrated Pest Management, Aarhus University [Aarhus], Evolutionary Ecology Group, Department Vertebrates, Institut Royal des Sciences Naturelles de Belgique (IRSNB), State University Center of Antwerp, Universiteit Antwerpen, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)
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taxonomy ,cytochrome b ,[SDV]Life Sciences [q-bio] ,Africa ,Dasymys ,[SDE]Environmental Sciences ,Rodentia ,craniometry ,phylogeny - Abstract
International audience; In an attempt to properly identify Dasymys specimens that were collected during the last decennia in the East-African region (Rwanda-Tanzania) we undertook a revision, of this genus. Although we initially limited our study area to central and eastern Africa, we were forced to include specimens for comparison from other areas, including western Africa, Angola and Zimbabwe-Zambia. This revision was realized using craniometric data of nearly 1000 skulls grouped in 20 operational taxonomical units (OTU's) mainly occurring in the central and eastern part of the African continent. The observation that differences in age and sex composition of the OTU's are of no or little consequence for the branching of the obtained phenetic trees, allowed us to undertake the screening of the genus Dasymys of the central and eastern African region. This approach enabled us to evaluate already described taxa, to select a neotype for D. nudipes and to describe three new taxa. Subsequent genetic analysis (cytochrome b) allowed us to provide a genetical characterization of two of the new species and several other taxa. Our phylogenetic analysis suggests that the genus Dasymys originated in the west African forest block betore spreading in a first step to the forest of the central African region and then in a second step to the savannahs of southern, eastern and possibly also western Africa.
- Published
- 2003
11. A craniometric and genetic description of two new species from the **Lophuromys flavopunctatus** THOMAS 1888 s.l. species complex (Rodentia - Muridae - Africa)
- Author
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Walter Verheyen, Jan Hulselmans, Dierckx, T., and ERIK VERHEYEN
- Published
- 2002
12. Relating to the ‘real’ Theories for and Experiences with Educational Database Systems
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Dierckx, T., primary, Stellingwerff, Martijn, additional, and Verbeke, Johan, additional
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- 2002
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13. Low viral richness at baseline in ulcerative ulcerative colitis associated with faecal microbiota transplantation success
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Conceicao-Neto, N., Deboutte, W., Dierckx, T., Machiels, K., Wang, J., Yinda, C., Maes, P., Marc Van Ranst, Joossens, M., Raes, J., Vermeire, S., and Matthijnssens, J.
14. Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes.
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Christensen KT, Pierard F, Bonsall D, Bowden R, Barnes E, Florence E, Ansari MA, Nguyen D, de Cesare M, Nevens F, Robaeys G, Schrooten Y, Busschots D, Simmonds P, Vandamme AM, Van Wijngaerden E, Dierckx T, Cuypers L, and Van Laethem K
- Subjects
- Male, Humans, Hepacivirus genetics, Phylogeny, Homosexuality, Male, Belgium epidemiology, High-Throughput Nucleotide Sequencing, Substance Abuse, Intravenous complications, HIV Infections, Sexual and Gender Minorities, Hepatitis C, HIV Seropositivity
- Abstract
The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium.
- Published
- 2023
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15. Extracellular vesicle-associated cholesterol supports the regenerative functions of macrophages in the brain.
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Vanherle S, Guns J, Loix M, Mingneau F, Dierckx T, Wouters F, Kuipers K, Vangansewinkel T, Wolfs E, Lins PP, Bronckaers A, Lambrichts I, Dehairs J, Swinnen JV, Verberk SGS, Haidar M, Hendriks JJA, and Bogie JFJ
- Subjects
- Brain, Macrophages, Cell Differentiation, Cholesterol, Extracellular Vesicles
- Abstract
Macrophages play major roles in the pathophysiology of various neurological disorders, being involved in seemingly opposing processes such as lesion progression and resolution. Yet, the molecular mechanisms that drive their harmful and benign effector functions remain poorly understood. Here, we demonstrate that extracellular vesicles (EVs) secreted by repair-associated macrophages (RAMs) enhance remyelination ex vivo and in vivo by promoting the differentiation of oligodendrocyte precursor cells (OPCs). Guided by lipidomic analysis and applying cholesterol depletion and enrichment strategies, we find that EVs released by RAMs show markedly elevated cholesterol levels and that cholesterol abundance controls their reparative impact on OPC maturation and remyelination. Mechanistically, EV-associated cholesterol was found to promote OPC differentiation predominantly through direct membrane fusion. Collectively, our findings highlight that EVs are essential for cholesterol trafficking in the brain and that changes in cholesterol abundance support the reparative impact of EVs released by macrophages in the brain, potentially having broad implications for therapeutic strategies aimed at promoting repair in neurodegenerative disorders., (© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
- Published
- 2023
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16. BMAL1 loss in oligodendroglia contributes to abnormal myelination and sleep.
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Rojo D, Dal Cengio L, Badner A, Kim S, Sakai N, Greene J, Dierckx T, Mehl LC, Eisinger E, Ransom J, Arellano-Garcia C, Gumma ME, Soyk RL, Lewis CM, Lam M, Weigel MK, Damonte VM, Yalçın B, Jones SE, Ollila HM, Nishino S, and Gibson EM
- Subjects
- Mice, Animals, Sleep Deprivation metabolism, Mice, Knockout, Oligodendroglia metabolism, Myelin Sheath metabolism, Sleep genetics, Cell Differentiation, ARNTL Transcription Factors genetics, Multiple Sclerosis metabolism
- Abstract
Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific proliferation, morphology, and BMAL1 are time-of-day dependent. Knockout of Bmal1 in mouse OPCs during development disrupts the expression of genes associated with circadian rhythms, proliferation, density, morphology, and migration, leading to changes in OPC dynamics in a spatiotemporal manner. Furthermore, these deficits translate into thinner myelin, dysregulated cognitive and motor functions, and sleep fragmentation. OPC-specific Bmal1 loss in adulthood does not alter OPC density at baseline but impairs the remyelination of a demyelinated lesion driven by changes in OPC morphology and migration. Lastly, we show that sleep fragmentation is associated with increased prevalence of the demyelinating disorder multiple sclerosis (MS), suggesting a link between MS and sleep that requires further investigation. These findings have broad mechanistic and therapeutic implications for brain disorders that include both myelin and sleep phenotypes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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17. Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation.
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Assone T, Menezes SM, de Toledo Gonçalves F, Folgosi VA, da Silva Prates G, Dierckx T, Braz M, Smid J, Haziot ME, Marcusso RMN, Dahy FE, Vanderlinden E, Claes S, Schols D, Bruhn R, Murphy EL, Penalva de Oliveira AC, Daelemans D, Vercauteren J, Casseb J, and Van Weyenbergh J
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- Female, Humans, Bayes Theorem, Cytokines, Human T-lymphotropic virus 1, Interleukin-17, Interleukin-6, Leukocytes, Mononuclear, Motor Disorders virology, Neuroinflammatory Diseases virology, HTLV-I Infections complications
- Abstract
Background: HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors., Patients and Methods: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and
1 NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification., Results: We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-γ (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-γ levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP., Conclusions: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-γ and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP., (© 2022. The Author(s).)- Published
- 2022
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18. Phloretin enhances remyelination by stimulating oligodendrocyte precursor cell differentiation.
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Dierckx T, Vanherle S, Haidar M, Grajchen E, Mingneau F, Gervois P, Wolfs E, Bylemans D, Voet A, Nguyen T, Hamad I, Kleinewietfeld M, Bogie JFJ, and Hendriks JJA
- Subjects
- Animals, Mice, Phloretin pharmacology, Mice, Inbred C57BL, Oligodendroglia, Cell Differentiation physiology, Myelin Sheath, Remyelination physiology, Oligodendrocyte Precursor Cells
- 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.
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- 2022
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19. The ApoA-I mimetic peptide 5A enhances remyelination by promoting clearance and degradation of myelin debris.
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Vanherle S, Jorissen W, Dierckx T, Loix M, Grajchen E, Mingneau F, Guns J, Gervois P, Lambrichts I, Dehairs J, Swinnen JV, Mulder MT, Remaley AT, Haidar M, Hendriks JJA, and Bogie JJF
- Subjects
- Humans, Myelin Sheath metabolism, Apolipoprotein A-I metabolism, Peptides metabolism, Remyelination physiology, Demyelinating Diseases metabolism
- 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 indicate that 5A promotes remyelination by stimulating clearance and degradation of myelin debris., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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20. Targeting lipophagy in macrophages improves repair in multiple sclerosis.
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Haidar M, Loix M, Vanherle S, Dierckx T, Vangansewinkel T, Gervois P, Wolfs E, Lambrichts I, Bogie JFJ, and Hendriks JJA
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- Humans, Trehalose metabolism, Macrophages metabolism, Lipopolysaccharides pharmacology, Lipopolysaccharides metabolism, Nitric Oxide Synthase Type II metabolism, Autophagy genetics, Multiple Sclerosis metabolism, Multiple Sclerosis pathology
- Abstract
Foamy macrophages containing abundant intracellular myelin remnants are an important pathological hallmark of multiple sclerosis. Reducing the intracellular lipid burden in foamy macrophages is considered a promising therapeutic strategy to induce a phagocyte phenotype that promotes central nervous system repair. Recent research from our group showed that sustained intracellular accumulation of myelin-derived lipids skews these phagocytes toward a disease-promoting and more inflammatory phenotype. Our data now demonstrate that disturbed lipophagy, a selective form of autophagy that helps with the degradation of lipid droplets, contributes to the induction of this phenotype. Stimulating autophagy using the natural disaccharide trehalose reduced the lipid load and inflammatory phenotype of myelin-laden macrophages. Importantly, trehalose was able to boost remyelination in the ex vivo brain slice model and the in vivo cuprizone-induced demyelination model. In summary, our results provide a molecular rationale for impaired metabolism of myelin-derived lipids in macrophages, and identify lipophagy induction as a promising treatment strategy to promote remyelination. Abbreviations: Baf: bafilomycin a1; BMDM: bone marrow-derived macrophage; CD68: CD68 antigen; CNS: central nervous system; LD: lipid droplet; LIPE/HSL: lipase, hormone sensitive; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MBP: myelin basic protein; MGLL: monoglyceride lipase; MS: multiple sclerosis; NO: nitric oxide; NOS2/iNOS: nitric oxide synthase 2, inducible; ORO: oil red o; PNPLA2: patatin-like phospholipase domain containing 2; PLIN2: perilipin 2; TEM: transmission electron microscopy; TFEB: transcription factor EB; TOH: trehalose.
- Published
- 2022
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21. Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort.
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Christensen KT, Pierard F, Beuselinck K, Bonsall D, Bowden R, Lagrou K, Nevens F, Schrooten Y, Simmonds P, Vandamme AM, Van Wijngaerden E, Dierckx T, Cuypers L, and Van Laethem K
- Subjects
- Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Belgium epidemiology, Drug Resistance, Viral genetics, Genotype, Hepacivirus genetics, High-Throughput Nucleotide Sequencing methods, Humans, Prevalence, Viral Nonstructural Proteins genetics, Hepatitis C drug therapy, Hepatitis C epidemiology, Hepatitis C, Chronic drug therapy
- Abstract
Background: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA)., Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping., Study Design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated., Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15))., Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping., Competing Interests: Declaration of Competing Interest The authors declare no commercial or financial relationship that could be construed as potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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22. Phloretin suppresses neuroinflammation by autophagy-mediated Nrf2 activation in macrophages.
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Dierckx T, Haidar M, Grajchen E, Wouters E, Vanherle S, Loix M, Boeykens A, Bylemans D, Hardonnière K, Kerdine-Römer S, Bogie JFJ, and Hendriks JJA
- Subjects
- Animals, Autophagy physiology, Cells, Cultured, Immunologic Factors pharmacology, Immunologic Factors therapeutic use, Inflammation Mediators antagonists & inhibitors, Inflammation Mediators metabolism, Macrophages metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-E2-Related Factor 2 deficiency, Phloretin therapeutic use, Autophagy drug effects, Encephalomyelitis, Autoimmune, Experimental drug therapy, Encephalomyelitis, Autoimmune, Experimental metabolism, Macrophages drug effects, NF-E2-Related Factor 2 metabolism, Phloretin pharmacology
- Abstract
Background: Macrophages play a dual role in neuroinflammatory disorders such as multiple sclerosis (MS). They are involved in lesion onset and progression but can also promote the resolution of inflammation and repair of damaged tissue. In this study, we investigate if and how phloretin, a flavonoid abundantly present in apples and strawberries, lowers the inflammatory phenotype of macrophages and suppresses neuroinflammation., Methods: Transcriptional changes in mouse bone marrow-derived macrophages upon phloretin exposure were assessed by bulk RNA sequencing. Underlying pathways related to inflammation, oxidative stress response and autophagy were validated by quantitative PCR, fluorescent and absorbance assays, nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice, western blot, and immunofluorescence. The experimental autoimmune encephalomyelitis (EAE) model was used to study the impact of phloretin on neuroinflammation in vivo and confirm underlying mechanisms., Results: We show that phloretin reduces the inflammatory phenotype of macrophages and markedly suppresses neuroinflammation in EAE. Phloretin mediates its effect by activating the Nrf2 signaling pathway. Nrf2 activation was attributed to 5' AMP-activated protein kinase (AMPK)-dependent activation of autophagy and subsequent kelch-like ECH-associated protein 1 (Keap1) degradation., Conclusions: This study opens future perspectives for phloretin as a therapeutic strategy for neuroinflammatory disorders such as MS., Trial Registration: Not applicable.
- Published
- 2021
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23. Urinary Peptides as Potential Non-Invasive Biomarkers for Lupus Nephritis: Results of the Peptidu-LUP Study.
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Tailliar M, Schanstra JP, Dierckx T, Breuil B, Hanouna G, Charles N, Bascands JL, Dussol B, Vazi A, Chiche L, Siwy J, Faguer S, Daniel L, Daugas E, Jourde-Chiche N, and On Behalf Of The Groupe Coopératif Sur le Lupus Rénal Gclr
- Abstract
Background : Lupus nephritis (LN) is a severe manifestation of Systemic Lupus Erythematosus (SLE). The therapeutic strategy relies on kidney biopsy (KB) results. We tested whether urinary peptidome analysis could non-invasively differentiate active from non-active LN. Design : Urinary samples were collected from 93 patients (55 with active LN and 38 with non-active LN), forming a discovery ( n = 42) and an independent validation ( n = 51) cohort. Clinical characteristics were collected at inclusion and prospectively for 24 months. The urinary peptidome was analyzed by capillary-electrophoresis coupled to mass-spectrometry, comparing active LN to non-active LN, and assessing chronic lesions and response to therapy. The value of previously validated prognostic (CKD273) and differential diagnostic (LN172) signatures was evaluated. Results: Urinary peptides could not discriminate between active and non-active LN or predict early response to therapy. Tubulo-interstitial fibrosis was correlated to the CKD273. The LN172 score identified 92.5% of samples as LN. Few patients developed new-onset CKD. Conclusions: We validated the CKD273 and LN172 classifiers but did not identify a robust signature that could predict active LN and replace KB. The value of urinary peptidome to predict long-term CKD, or renal flares in SLE, remains to be evaluated.
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- 2021
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24. XPO1 inhibitors represent a novel therapeutic option in Adult T-cell Leukemia, triggering p53-mediated caspase-dependent apoptosis.
- Author
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Boons E, Nogueira TC, Dierckx T, Menezes SM, Jacquemyn M, Tamir S, Landesman Y, Farré L, Bittencourt A, Kataoka K, Ogawa S, Snoeck R, Andrei G, Van Weyenbergh J, and Daelemans D
- Subjects
- Antineoplastic Agents pharmacology, Cell Line, Tumor, Humans, Karyopherins metabolism, Leukemia-Lymphoma, Adult T-Cell metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Exportin 1 Protein, Apoptosis drug effects, Hydrazines pharmacology, Karyopherins antagonists & inhibitors, Leukemia-Lymphoma, Adult T-Cell drug therapy, Receptors, Cytoplasmic and Nuclear antagonists & inhibitors, Triazoles pharmacology, Tumor Suppressor Protein p53 metabolism
- Published
- 2021
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25. enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9.
- Author
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Neggers JE, Jacquemyn M, Dierckx T, Kleinstiver BP, Thibaut HJ, and Daelemans D
- Subjects
- Binding Sites, Protein Binding, CRISPR-Cas Systems, Clustered Regularly Interspaced Short Palindromic Repeats, Drug Resistance genetics, Endonucleases metabolism, Genetic Testing methods, Mutation
- Abstract
While drug resistance mutations provide the gold standard proof for drug target engagement, target deconvolution of inhibitors identified from a phenotypic screen remains challenging. Genetic screening for functional in-frame drug resistance mutations by tiling CRISPR-Cas nucleases across protein coding sequences is a method for identifying a drug's target and binding site. However, the applicability of this approach is constrained by the availability of nuclease target sites across genetic regions that mediate drug resistance upon mutation. In this study, we show that an enhanced AsCas12a variant (enAsCas12a), which harbors an expanded targeting range, facilitates screening for drug resistance mutations with increased activity and resolution in regions that are not accessible to other CRISPR nucleases, including the prototypical SpCas9. Utilizing enAsCas12a, we uncover new drug resistance mutations against inhibitors of NAMPT and KIF11. These findings demonstrate that enAsCas12a is a promising new addition to the CRISPR screening toolbox and allows targeting sites not readily accessible to SpCas9., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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26. Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis.
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Wouters E, Grajchen E, Jorissen W, Dierckx T, Wetzels S, Loix M, Tulleners MP, Staels B, Stinissen P, Haidar M, Bogie JFJ, and Hendriks JJA
- Subjects
- Cells, Cultured, Humans, Multiple Sclerosis, Relapsing-Remitting genetics, Multiple Sclerosis, Relapsing-Remitting pathology, Myelin Sheath metabolism, PPAR gamma genetics, Foam Cells metabolism, Multiple Sclerosis, Relapsing-Remitting metabolism, PPAR gamma metabolism
- Abstract
Macrophages play a crucial role during the pathogenesis of multiple sclerosis (MS), a neuroinflammatory autoimmune disorder of the central nervous system. Important regulators of the metabolic and inflammatory phenotype of macrophages are liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). Previously, it has been reported that PPARγ expression is decreased in peripheral blood mononuclear cells of MS patients. The goal of the present study was to determine to what extent PPARγ , as well as the closely related nuclear receptors PPARα and β and LXRα and β , are differentially expressed in monocytes from MS patients and how this change in expression affects the function of monocyte-derived macrophages. We demonstrate that monocytes of relapsing-remitting MS patients display a marked decrease in PPARγ expression, while the expression of PPARα and LXRα/β is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in PPARγ expression. While a reduced PPARγ expression did not affect the inflammatory and phagocytic properties of myelin-loaded macrophages, it did impact myelin processing by increasing the intracellular cholesterol load of myelin-phagocytosing macrophages. Collectively, our findings indicate that an inflammation-induced reduction in PPARγ expression promotes myelin-induced foam cell formation in macrophages in MS.
- Published
- 2020
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27. CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation.
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Grajchen E, Wouters E, van de Haterd B, Haidar M, Hardonnière K, Dierckx T, Van Broeckhoven J, Erens C, Hendrix S, Kerdine-Römer S, Hendriks JJA, and Bogie JFJ
- Subjects
- Animals, Encephalomyelitis, Autoimmune, Experimental metabolism, Encephalomyelitis, Autoimmune, Experimental pathology, Female, Inflammation metabolism, Inflammation pathology, Mice, Mice, Inbred C57BL, CD36 Antigens metabolism, Macrophages metabolism, Microglia metabolism, Myelin Sheath metabolism, Phagocytosis physiology
- Abstract
Background: The presence of foamy macrophages and microglia containing intracellular myelin remnants is a pathological hallmark of neurodegenerative disorders such as multiple sclerosis (MS). Despite the importance of myelin internalization in affecting both central nervous system repair and neuroinflammation, the receptors involved in myelin clearance and their impact on the phagocyte phenotype and lesion progression remain to be clarified., Methods: Flow cytometry, quantitative PCR, and immunohistochemistry were used to define the mRNA and protein abundance of CD36 in myelin-containing phagocytes. The impact of CD36 and nuclear factor erythroid 2-related factor 2 (NRF2) on the phagocytic and inflammatory features of macrophages and microglia was assessed using a pharmacological CD36 inhibitor (sulfo-N-succinimidyl oleate) and Nrf2
-/- bone marrow-derived macrophages. Finally, the experimental autoimmune encephalomyelitis (EAE) model was used to establish the impact of CD36 inhibition on neuroinflammation and myelin phagocytosis in vivo., Results: Here, we show that the fatty acid translocase CD36 is required for the uptake of myelin debris by macrophages and microglia, and that myelin internalization increased CD36 expression through NRF2. Pharmacological inhibition of CD36 promoted the inflammatory properties of myelin-containing macrophages and microglia in vitro, which was paralleled by a reduced activity of the anti-inflammatory lipid-sensing liver X receptors and peroxisome proliferator-activated receptors. By using the EAE model, we provide evidence that CD36 is essential for myelin debris clearance in vivo. Importantly, CD36 inhibition markedly increased the neuroinflammatory burden and disease severity in the EAE model., Conclusion: Altogether, we show for the first time that CD36 is crucial for clearing myelin debris and suppressing neuroinflammation in demyelinating disorders such as MS.- Published
- 2020
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28. Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain.
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Bogie JFJ, Grajchen E, Wouters E, Corrales AG, Dierckx T, Vanherle S, Mailleux J, Gervois P, Wolfs E, Dehairs J, Van Broeckhoven J, Bowman AP, Lambrichts I, Gustafsson JÅ, Remaley AT, Mulder M, Swinnen JV, Haidar M, Ellis SR, Ntambi JM, Zelcer N, and Hendriks JJA
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, Animals, Cell Line, Cholesterol metabolism, Endocytosis, Fatty Acids metabolism, Foam Cells metabolism, Humans, Inflammation pathology, Macrophages metabolism, Macrophages ultrastructure, Mice, Microglia metabolism, Myelin Sheath metabolism, Phagocytes pathology, Phagocytes ultrastructure, Phenotype, Protein Kinase C-delta metabolism, Stearoyl-CoA Desaturase deficiency, Brain pathology, Macrophages enzymology, Microglia enzymology, Stearoyl-CoA Desaturase metabolism
- Abstract
Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Bogie et al.)
- Published
- 2020
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29. Serum GlycA Level is Elevated in Active Systemic Lupus Erythematosus and Correlates to Disease Activity and Lupus Nephritis Severity.
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Dierckx T, Chiche L, Daniel L, Lauwerys B, Weyenbergh JV, and Jourde-Chiche N
- Abstract
Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement., Methods: Serum GlycA was measured by nuclear magnetic resonance spectroscopy in samples from well characterized SLE patients and from both healthy controls and patients with other kidney diseases (KD). Disease activity was evaluated using the Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K). Renal severity was assessed by kidney biopsy., Results: Serum GlycA was elevated in active (n = 105) compared to quiescent SLE patients (n = 39, p < 10
-6 ), healthy controls (n = 20, p = 0.009) and KD controls (n = 21, p = 0.04), despite a more severely altered renal function in the latter. GlycA level was correlated to disease activity (SLEDAI-2K, ρ = 0.37, p < 10-4 ), Creactive protein, neutrophil count, triglyceride levels, proteinuria and inversely to serum albumin. In patients with biopsy-proven lupus nephritis (LN), GlycA levels were higher in proliferative (n = 26) than non-proliferative LN (n = 10) in univariate analysis (p = 0.04), and was shown to predict proliferative LN independently of renal parameters, immunological activity, neutrophil count and daily corticosteroid dosage by multivariate analysis (p < 5 × 10-3 for all models). In LN patients with repeated longitudinal GlycA measurement (n = 11), GlycA varied over time and seemed to peak at the time of the flare., Conclusions: GlycA, as a summary measure for different inflammatory processes, could be a valuable biomarker of disease activity in patients with SLE, and a non-invasive biomarker of pathological severity in the context of LN., Competing Interests: The authors declare no competing interests.- Published
- 2020
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30. An evolutionary recent IFN/IL-6/CEBP axis is linked to monocyte expansion and tuberculosis severity in humans.
- Author
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Delgobo M, Mendes DA, Kozlova E, Rocha EL, Rodrigues-Luiz GF, Mascarin L, Dias G, Patrício DO, Dierckx T, Bicca MA, Bretton G, Tenório de Menezes YK, Starick MR, Rovaris D, Del Moral J, Mansur DS, Van Weyenbergh J, and Báfica A
- Subjects
- Antigens, CD34, CCAAT-Enhancer-Binding Proteins genetics, Cell Differentiation, Cell Proliferation, Cytokines genetics, Cytokines metabolism, Genome-Wide Association Study, Humans, Hydrolases, Interferons genetics, Interleukin-6 genetics, Macrophages microbiology, Monocytes microbiology, Mycobacterium tuberculosis pathogenicity, Myeloid Cells physiology, Proteomics, Receptors, Interleukin-6, Severity of Illness Index, Transcriptome, Tuberculosis metabolism, CCAAT-Enhancer-Binding Proteins metabolism, Interferons metabolism, Interleukin-6 metabolism, Monocytes metabolism, Mycobacterium tuberculosis immunology, Tuberculosis immunology
- Abstract
Monocyte counts are increased during human tuberculosis (TB) but it has not been determined whether Mycobacterium tuberculosis ( Mtb ) directly regulates myeloid commitment. We demonstrated that exposure to Mtb directs primary human CD34
+ cells to differentiate into monocytes/macrophages. In vitro myeloid conversion did not require type I or type II IFN signaling. In contrast, Mtb enhanced IL-6 responses by CD34+ cell cultures and IL-6R neutralization inhibited myeloid differentiation and decreased mycobacterial growth in vitro. Integrated systems biology analysis of transcriptomic, proteomic and genomic data of large data sets of healthy controls and TB patients established the existence of a myeloid IL-6/IL6R/CEBP gene module associated with disease severity. Furthermore, genetic and functional analysis revealed the IL6/IL6R/CEBP gene module has undergone recent evolutionary selection, including Neanderthal introgression and human pathogen adaptation, connected to systemic monocyte counts. These results suggest Mtb co-opts an evolutionary recent IFN-IL6-CEBP feed-forward loop, increasing myeloid differentiation linked to severe TB in humans., Competing Interests: MD, DM, EK, ER, GR, LM, GD, DP, TD, MB, GB, YT, MS, DR, JD, DM, JV, AB No competing interests declared, (© 2019, Delgobo et al.)- Published
- 2019
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31. Decreased RORC expression and downstream signaling in HTLV-1-associated adult T-cell lymphoma/leukemia uncovers an antiproliferative IL17 link: A potential target for immunotherapy?
- Author
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Subramanian K, Dierckx T, Khouri R, Menezes SM, Kagdi H, Taylor GP, Farre L, Bittencourt A, Kataoka K, Ogawa S, and Van Weyenbergh J
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Basic-Leucine Zipper Transcription Factors genetics, Cell Adhesion Molecule-1 genetics, Cohort Studies, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Middle Aged, Proliferating Cell Nuclear Antigen genetics, Retroviridae Proteins genetics, Young Adult, Down-Regulation, Interleukin-17 genetics, Leukemia-Lymphoma, Adult T-Cell genetics, Nuclear Receptor Subfamily 1, Group F, Member 3 genetics, Signal Transduction
- Abstract
Retinoic acid-related drugs have shown promising pre-clinical activity in Adult T-cell Leukemia/Lymphoma, but RORC signaling has not been explored. Therefore, we investigated transcriptome-wide interactions of the RORC pathway in HTLV-1 and ATL, using our own and publicly available gene expression data for ATL and other leukemias. Gene expression data from ATL patients were analyzed using WGCNA to determine gene modules and their correlation to clinical and molecular data. Both PBMCs and CD4
+ T-Cells exhibited decreased RORC expression in four different ATL cohorts. A small subset of RORChi ATL patients was identified with significantly lower pathognomonic CADM1 and HBZ levels but similar levels of other ATL markers (CD4/CD25/CCR4), hinting at a less aggressive ATL subtype. An age-dependent decrease in RORC expression was found in HTLV-1-infected individuals, but not in healthy controls, suggesting an early molecular event predisposing to leukemogenesis. Genes upstream of RORC signaling were members of a proliferative gene module (containing proliferation markers PCNA/Ki67), whereas downstream members clustered in an anti-proliferative gene module. IL17C transcripts showed the strongest negative correlation to PCNA in both ATL cohorts, which was replicated in two large cohorts of T- and B-cell acute lymphoid leukemia (ALL). Finally, IL17C expression in purified CD4 + CCR4 + CD26-CD7- "ATL-like" cells from HTLV-1-infected individuals and ATL patients was negatively correlated with clonality, underscoring a possible antileukemic/antiproliferative role. In conclusion, decreased RORC expression and downstream signaling might represent an early event in ATL pathogenesis. An antiproliferative IL17C/PCNA link is shared between ATL, T-ALL and B-ALL, suggesting (immuno)therapeutic benefit of boosting RORC/IL17 signaling., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)- Published
- 2019
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32. GlycA, a Nuclear Magnetic Resonance Spectroscopy Measure for Protein Glycosylation, is a Viable Biomarker for Disease Activity in IBD.
- Author
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Dierckx T, Verstockt B, Vermeire S, and van Weyenbergh J
- Subjects
- Acetylation, Adult, Biomarkers blood, C-Reactive Protein metabolism, Case-Control Studies, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Endoscopy, Gastrointestinal, Feces chemistry, Female, Glycosylation, Humans, Intestinal Mucosa pathology, Leukocyte L1 Antigen Complex metabolism, Magnetic Resonance Spectroscopy, Male, Middle Aged, Prospective Studies, Young Adult, Colitis, Ulcerative blood, Crohn Disease blood, Glycoproteins blood
- Abstract
Background and Aims: Glycoprotein acetylation [GlycA] is a novel nuclear magnetic resonance [NMR] biomarker, measured in serum or plasma, that summarizes the signals originating from glycan groups of certain acute-phase glycoproteins. This biomarker has been shown to be robustly associated with cardiovascular and short-term all-cause mortality, and with disease severity in several inflammatory conditions. We investigated GlycA levels in a cohort of healthy individuals [HCs], patients with Crohn's disease [CD] and patients with ulcerative colitis [UC] prior to and after therapeutic control of inflammation., Methods: Serum samples of 10 HCs, 37 CD patients and 21 UC patients before and after biologic therapy were subjected to high-throughput NMR analysis by Nightingale Health Ltd. Paired C-reactive protein [CRP] and fecal calprotectin [fCal] measurements were used to characterize baseline differences, treatment effects and post-treatment association with endoscopic response [50% SES-CD decrease at Week 24] and mucosal healing [SES-CD ≤ 2 for CD, Mayo endoscopic score ≤ 1 for UC]., Results: GlycA levels were significantly higher in patients with active inflammamtory bowel disease [IBD] compared with those in healthy controls, and accurately reflected the mucosal recovery to a 'healthy' state in both CD and UC patients achieving mucosal healing. In CD patients who experienced an endoscopic response without achieving full mucosal healing, GlycA levels also decreased but did not normalize to HC levels. Overall, GlycA correlated well with CRP and fCal, and accurately tracked disease activity in CRP-negative patients [<5 mg/dL]., Conclusion: GlycA holds promise as a viable serological biomarker for disease activity in IBD, even in patients without elevated CRP, and should therefore be tested in large prospective cohorts., (© European Crohn’s and Colitis Organisation (ECCO) 2018.)
- Published
- 2019
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33. The Impact of Phytosterols on the Healthy and Diseased Brain.
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Dierckx T, Bogie JFJ, and Hendriks JJA
- Subjects
- Animals, Humans, Molecular Structure, Phytosterols chemistry, Phytosterols metabolism, Central Nervous System drug effects, Central Nervous System Diseases drug therapy, Phytosterols pharmacology
- Abstract
The central nervous system (CNS) is the most cholesterol-rich organ in mammals. Cholesterol homeostasis is essential for proper brain functioning and dysregulation of cholesterol metabolism can lead to neurological problems. Multiple sclerosis (MS) and Alzheimer's disease (AD) are examples of neurological diseases that are characterized by a disturbed cholesterol metabolism. Phytosterols (PS) are plant-derived components that structurally and functionally resemble cholesterol. PS are known for their cholesterol-lowering properties. Due to their ability to reach the brain, researchers have started to investigate the physiological role of PS in the CNS. In this review, the metabolism and function of PS in the diseased and healthy CNS are discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2019
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34. In situ Immune Signatures and Microbial Load at the Nasopharyngeal Interface in Children With Acute Respiratory Infection.
- Author
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Fukutani KF, Nascimento-Carvalho CM, Bouzas ML, Oliveira JR, Barral A, Dierckx T, Khouri R, Nakaya HI, Andrade BB, Van Weyenbergh J, and de Oliveira CI
- Abstract
Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus- and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial ( n = 27), viral ( n = 5), codetection [containing both viral and bacterial transcripts ( n = 21), or indeterminate intermediate where microbial load is below threshold ( n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ "snapshot" of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling.
- Published
- 2018
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35. Low eukaryotic viral richness is associated with faecal microbiota transplantation success in patients with UC.
- Author
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Conceição-Neto N, Deboutte W, Dierckx T, Machiels K, Wang J, Yinda KC, Maes P, Van Ranst M, Joossens M, Raes J, Vermeire S, and Matthijnssens J
- Subjects
- Colitis, Ulcerative, Feces, Humans, Eukaryota, Fecal Microbiota Transplantation
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2018
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36. Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation.
- Author
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Leal FE, Menezes SM, Costa EAS, Brailey PM, Gama L, Segurado AC, Kallas EG, Nixon DF, Dierckx T, Khouri R, Vercauteren J, Galvão-Castro B, Saraiva Raposo RA, and Van Weyenbergh J
- Abstract
HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this "IFN paradox" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4
+ T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax), proviral load and 42 host genes with known antiretroviral (anti-HIV) activity in purified CD4+ T cells. This revealed two major clusters ("antiviral/protective" vs. "proviral/deleterious"), as evidenced by significant negative (TRIM5/TRIM22/BST2) vs. positive correlation (ISG15/PAF1/CDKN1A) with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H), underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2) were significantly up-regulated by IFN-β, but not IFN-α, in HAM/TSP. This was paralleled by a significant decrease in lymphoproliferation by IFN-β, but not IFN-α treatment. Finally, using published ex vivo whole blood transcriptomic data of independent cohorts, we validated the significant positive correlation between TRIM5, TRIM22, and BST2 in HTLV-1-infected individuals and HAM/TSP patients, which was independent of the HAM/TSP disease signature. In conclusion, our results provide ex vivo mechanistic evidence for the observed immunovirological effect of in vivo IFN-β treatment in HAM/TSP, reconcile an apparent IFN paradox in HTLV-1 research and identify biomarkers/targets for a precision medicine approach.- Published
- 2018
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37. ISG15-Induced IL-10 Is a Novel Anti-Inflammatory Myeloid Axis Disrupted during Active Tuberculosis.
- Author
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Dos Santos PF, Van Weyenbergh J, Delgobo M, Oliveira Patricio D, Ferguson BJ, Guabiraba R, Dierckx T, Menezes SM, Báfica A, and Mansur DS
- Subjects
- Humans, Cytokines immunology, Interleukin-10 immunology, Leukocytes, Mononuclear immunology, Tuberculosis immunology, Ubiquitins immunology
- Abstract
IFN-stimulated gene 15 (ISG15) deficiency in humans leads to severe IFNopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. In this study, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. A balanced ISG15-induced monocyte/IL-10 versus lymphoid/IFN-γ expression, correlating with p38 MAPK and PI3K signaling, was found using targeted in vitro and ex vivo systems analysis of human transcriptomic datasets. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmed in vitro using CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, this ISG15/IL-10 axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB, suggesting its potential use as a biomarker, awaiting clinical validation. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB., (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Published
- 2018
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38. A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients.
- Author
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Khouri R, Silva-Santos G, Dierckx T, Menezes SM, Decanine D, Theys K, Silva AC, Farré L, Bittencourt A, Mangino M, Roederer M, Vandamme AM, and Van Weyenbergh J
- Abstract
Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4
+ CD25+ leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN + AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (TSCM ) Fashi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied. In this study, we found significant ex vivo antiproliferative, antiviral and immunomodulatory effects of IFN-α treatment in short-term culture of primary mononuclear cells from ATL patients (n = 25). Bayesian Network analysis allowed us to integrate ex vivo IFN-α response with clinical, genetic and immunological data from ATL patients, thereby revealing a central role for FAS -670 polymorphism and apoptosis in the coordinated mechanism of action of IFN-α. FAS genotype-dependence of IFN-induced apoptosis was experimentally validated in an independent cohort of healthy controls (n = 20). The same FAS -670 polymorphism also determined CD4 TSCM levels in a genome-wide twin study (p = 7 × 10-11 , n = 460), confirming a genetic link between apoptosis and TSCM levels. Transcriptomic analysis and cell type deconvolution confirmed the FAS genotype/TSCM link and IFN-α-induced downregulation of CD4 TSCM -specific genes in ATL patient cells. In conclusion, ex vivo IFN-α treatment exerts a pleiotropic effect on primary ATL cells, with a genetic IFN/STAT1/Fas axis determining apoptosis vs. proliferation and underscoring the CD4 TSCM model of ATL leukemogenesis.- Published
- 2018
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39. Target identification of small molecules using large-scale CRISPR-Cas mutagenesis scanning of essential genes.
- Author
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Neggers JE, Kwanten B, Dierckx T, Noguchi H, Voet A, Bral L, Minner K, Massant B, Kint N, Delforge M, Vercruysse T, Baloglu E, Senapedis W, Jacquemyn M, and Daelemans D
- Subjects
- Acrylamides pharmacology, Aminopyridines pharmacology, Antineoplastic Agents pharmacology, Cell Line, Cell Survival drug effects, Cell Survival genetics, Drug Resistance genetics, HCT116 Cells, HL-60 Cells, Humans, K562 Cells, Nicotinamide Phosphoribosyltransferase antagonists & inhibitors, Nicotinamide Phosphoribosyltransferase genetics, CRISPR-Cas Systems, Genes, Essential genetics, Molecular Targeted Therapy methods, Mutagenesis, Site-Directed methods, Small Molecule Libraries pharmacology
- Abstract
Unraveling the mechanism of action and molecular target of small molecules remains a major challenge in drug discovery. While many cancer drugs target genetic vulnerabilities, loss-of-function screens fail to identify essential genes in drug mechanism of action. Here, we report CRISPRres, a CRISPR-Cas-based genetic screening approach to rapidly derive and identify drug resistance mutations in essential genes. It exploits the local genetic variation created by CRISPR-Cas-induced non-homologous end-joining (NHEJ) repair to generate a wide variety of functional in-frame mutations. Using large sgRNA tiling libraries and known drug-target pairs, we validate it as a target identification approach. We apply CRISPRres to the anticancer agent KPT-9274 and identify nicotinamide phosphoribosyltransferase (NAMPT) as its main target. These results present a powerful and simple genetic approach to create many protein variants that, in combination with positive selection, can be applied to reveal the cellular target of small-molecule inhibitors.
- Published
- 2018
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40. Systems Approach Reveals Nuclear Factor Erythroid 2-Related Factor 2/Protein Kinase R Crosstalk in Human Cutaneous Leishmaniasis.
- Author
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Vivarini ÁC, Calegari-Silva TC, Saliba AM, Boaventura VS, França-Costa J, Khouri R, Dierckx T, Dias-Teixeira KL, Fasel N, Barral AMP, Borges VM, Van Weyenbergh J, and Lopes UG
- Abstract
Leishmania parasites infect macrophages, causing a wide spectrum of human diseases, from cutaneous to visceral forms. In search of novel therapeutic targets, we performed comprehensive in vitro and ex vivo mapping of the signaling pathways upstream and downstream of antioxidant transcription factor [nuclear factor erythroid 2-related factor 2 (Nrf2)] in cutaneous leishmaniasis (CL), by combining functional assays in human and murine macrophages with a systems biology analysis of in situ (skin biopsies) CL patient samples. First, we show the PKR pathway controls the expression and activation of Nrf2 in Leishmania amazonensis infection in vitro . Nrf2 activation also required PI3K/Akt signaling and autophagy mechanisms. Nrf2- or PKR/Akt-deficient macrophages exhibited increased levels of ROS/RNS and reduced expression of Sod1 Nrf2-dependent gene and reduced parasite load. L. amazonensis counteracted the Nrf2 inhibitor Keap1 through the upregulation of p62 via PKR. This Nrf2/Keap1 observation was confirmed in situ in skin biopsies from Leishmania -infected patients. Next, we explored the ex vivo transcriptome in CL patients, as compared to healthy controls. We found the antioxidant response element/Nrf2 signaling pathway was significantly upregulated in CL, including downstream target p62. In silico enrichment analysis confirmed upstream signaling by interferon and PI3K/Akt, and validated our in vitro findings. Our integrated in vitro, ex vivo , and in silico approach establish Nrf2 as a central player in human cutaneous leishmaniasis and reveal Nrf2/PKR crosstalk and PI3K/Akt pathways as potential therapeutic targets.
- Published
- 2017
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41. A Fas hi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.
- Author
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Menezes SM, Leal FE, Dierckx T, Khouri R, Decanine D, Silva-Santos G, Schnitman SV, Kruschewsky R, López G, Alvarez C, Talledo M, Gotuzzo E, Nixon DF, Vercauteren J, Brassat D, Liblau R, Vandamme AM, Galvão-Castro B, and Van Weyenbergh J
- Abstract
Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas
hi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fashi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating biased, but not defective Fas signaling in HAM/TSP. In silico analysis revealed biased Fas signaling toward proliferation and inflammation, driven by RelA/NF-κB. Correlation of Fas transcript levels with proliferation (but not apoptosis) was confirmed in HAM/TSP ex vivo transcriptomes. In conclusion, we demonstrated a two-step increase in Fas expression, revealing a unique Fashi lymphocyte phenotype in HAM/TSP, distinguishable from MS. Non-apoptotic Fas signaling might fuel HAM/TSP pathogenesis, through increased lymphoproliferation, inflammation, and early age of onset.- Published
- 2017
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42. Inflammatory Gene Expression Profile and Defective Interferon-γ and Granzyme K in Natural Killer Cells From Systemic Juvenile Idiopathic Arthritis Patients.
- Author
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Put K, Vandenhaute J, Avau A, van Nieuwenhuijze A, Brisse E, Dierckx T, Rutgeerts O, Garcia-Perez JE, Toelen J, Waer M, Leclercq G, Goris A, Van Weyenbergh J, Liston A, De Somer L, Wouters CH, and Matthys P
- Subjects
- Arthritis, Juvenile genetics, Cells, Cultured, Gene Expression, Humans, Phenotype, Arthritis, Juvenile immunology, Granzymes genetics, Interferon-gamma genetics, Killer Cells, Natural physiology
- Abstract
Objective: Systemic juvenile idiopathic arthritis (JIA) is an immunoinflammatory disease characterized by arthritis and systemic manifestations. The role of natural killer (NK) cells in the pathogenesis of systemic JIA remains unclear. The purpose of this study was to perform a comprehensive analysis of NK cell phenotype and functionality in patients with systemic JIA., Methods: Transcriptional alterations specific to NK cells were investigated by RNA sequencing of highly purified NK cells from 6 patients with active systemic JIA and 6 age-matched healthy controls. Cytokines (NK cell-stimulating and others) were quantified in plasma samples (n = 18). NK cell phenotype and cytotoxic activity against tumor cells were determined (n = 10), together with their interferon-γ (IFNγ)-producing function (n = 8)., Results: NK cells from the systemic JIA patients showed an altered gene expression profile compared to cells from the healthy controls, with enrichment of immunoinflammatory pathways, increased expression of innate genes including TLR4 and S100A9, and decreased expression of immune-regulating genes such as IL10RA and GZMK. In the patients' plasma, interleukin-18 (IL-18) levels were increased, and a decreased ratio of IFNγ to IL-18 was observed. NK cells from the patients exhibited specific alterations in the balance of inhibitory and activating receptors, with decreased killer cell lectin-like receptor G1 and increased NKp44 expression. Although NK cells from the patients showed increased granzyme B expression, consistent with intact cytotoxicity and degranulation against a tumor cell line, decreased granzyme K expression in CD56
bright NK cells and defective IL-18-induced IFNγ production and signaling were demonstrated., Conclusion: NK cells are active players in the inflammatory environment typical of systemic JIA. Although their cytotoxic function is globally intact, subtle defects in NK-related pathways, such as granzyme K expression and IL-18-driven IFNγ production, may contribute to the immunoinflammatory dysregulation in this disease., (© 2016, American College of Rheumatology.)- Published
- 2017
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43. Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naïve Patients.
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Marascio N, Pavia G, Strazzulla A, Dierckx T, Cuypers L, Vrancken B, Barreca GS, Mirante T, Malanga D, Oliveira DM, Vandamme AM, Torti C, Liberto MC, and Focà A
- Subjects
- Drug Resistance, Viral genetics, High-Throughput Nucleotide Sequencing, Humans, Mutation, Oligopeptides pharmacology, Proline analogs & derivatives, Proline pharmacology, Simeprevir pharmacology, Viral Nonstructural Proteins genetics, Antiviral Agents pharmacology, Hepacivirus drug effects, Hepacivirus genetics
- Abstract
Naturally occurring resistance-associated substitutions (RASs) can negatively impact the response to direct-acting antivirals (DAAs) agents-based therapies for hepatitis C virus (HCV) infection. Herein, we set out to characterize the RASs in the HCV1b genome from serum samples of DAA-naïve patients in the context of the SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology, 2014) project. We deep-sequenced the NS3/4A protease region of the viral population using the Ion Torrent Personal Genome Machine, and patient-specific majority rule consensus sequence summaries were constructed with a combination of freely available next generation sequencing data analysis software. We detected NS3/4A protease major and minor variants associated with resistance to boceprevir (V36L), telaprevir (V36L, I132V), simeprevir (V36L), and grazoprevir (V36L, V170I). Furthermore, we sequenced part of HCV NS5B polymerase using Sanger-sequencing and detected a natural RAS for dasabuvir (C316N). This mutation could be important for treatment strategies in cases of previous therapy failure., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
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44. Pathogen transcriptional profile in nasopharyngeal aspirates of children with acute respiratory tract infection.
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Fukutani KF, Nascimento-Carvalho CM, Van der Gucht W, Wollants E, Khouri R, Dierckx T, Van Ranst M, Houspie L, Bouzas ML, Oliveira JR, Barral A, Van Weyenbergh J, and de Oliveira CI
- Subjects
- Bacteria classification, Bacteria isolation & purification, Bacterial Infections diagnosis, Humans, Infant, Multiplex Polymerase Chain Reaction methods, Nasopharynx microbiology, Phylogeny, Respiratory Tract Infections diagnosis, Sensitivity and Specificity, Virus Diseases diagnosis, Viruses classification, Viruses isolation & purification, Bacteria genetics, Gene Expression Profiling methods, RNA, Bacterial analysis, RNA, Viral analysis, Respiratory Tract Infections microbiology, Viruses genetics
- Abstract
Background: Acute respiratory tract infections (ARI) present a significant morbidity and pose a global health burden. Patients are frequently treated with antibiotics although ARI are most commonly caused by virus, strengthening the need for improved diagnostic methods., Objectives: Detect viral and bacterial RNA in nasopharyngeal aspirates (NPA) from children aged 6-23 months with ARI using nCounter., Study Design: A custom-designed nCounter probeset containing viral and bacterial targets was tested in NPA of ARI patients., Results: Initially, spiked control viral RNAs were detectable in ≥6.25 ng input RNA, indicating absence of inhibitors in NPA. nCounter applied to a larger NPA sample (n=61) enabled the multiplex detection of different pathogens: RNA viruses Parainfluenza virus (PIV 1-3) and RSV A-B in 21%, Human metapneumovirus (hMPV) in 5%, Bocavirus (BoV), CoV, Influenza virus (IV) A in 3% and, Rhinovirus (RV) in 2% of samples, respectively. RSV A-B was confirmed by Real Time PCR (86.2-96.9% agreement). DNA virus (AV) was detected at RNA level, reflecting viral replication, in 10% of samples. Bacterial transcripts from Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydophila pneumoniae were detected in 77, 69, 26, 8, 3 and 2% of samples, respectively., Conclusion: nCounter is robust and sensitive for the simultaneous detection of viral (both RNA and DNA) and bacterial transcripts in NPA with low RNA input (<10 ng). This medium-throughput technique will increase our understanding of ARI pathogenesis and may provide an evidence-based approach for the targeted and rational use of antibiotics in pediatric ARI., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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45. An electrochemical impedimetric aptasensing platform for sensitive and selective detection of small molecules such as chloramphenicol.
- Author
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Pilehvar S, Dierckx T, Blust R, Breugelmans T, and De Wael K
- Subjects
- Anti-Bacterial Agents analysis, Anti-Bacterial Agents chemistry, Chloramphenicol chemistry, Equipment Design, Equipment Failure Analysis, Molecular Weight, Reproducibility of Results, Sensitivity and Specificity, Aptamers, Nucleotide chemistry, Biosensing Techniques instrumentation, Chloramphenicol analysis, Food Analysis instrumentation, Food Contamination analysis
- Abstract
We report on the aptadetection of chloramphenicol (CAP) using electrochemical impedance spectroscopy. The detection principle is based on the changes of the interfacial properties of the electrode after the interaction of the ssDNA aptamers with the target molecules. The electrode surface is partially blocked due to the formation of the aptamer-CAP complex, resulting in an increase of the interfacial electron-transfer resistance of the redox probe detected by electrochemical impedance spectroscopy or cyclic voltammetry. We observed that the ratio of polarization resistance had a linear relationship with the concentrations of CAP in the range of 1.76-127 nM, and a detection limit of 1.76 nM was obtained. The covalent binding of CAP-aptamer on the electrode surface combined with the unique properties of aptamers and impedimetric transduction leads to the development of a stable and sensitive electrochemical aptasensor for CAP.
- Published
- 2014
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