-
1دورية أكاديمية
المؤلفون: Gonzalez-Moro, Itziar, Garcia-Etxebarria, Koldo G-E, K, Mendoza, Luis Manuel M LM, Fernández-Jiménez, Nora FJN, Mentxaka, Jon MJ, Olazagoitia-Garmendia, Ane, Arroyo, Maria Nicol, Sawatani, Toshiaki, Moreno Castro, Cristina, Vinci, Chiara, Op De Beeck, Anne, Cnop, Miriam, Igoillo Esteve, Mariana, Santin, Izortze
المصدر: Advanced Science
مصطلحات موضوعية: Sciences bio-médicales et agricoles, Sciences biomédicales
الوصف: Type 1 diabetes (T1D) is a complex autoimmune disease that develops in genetically susceptible individuals. Most T1D-associated single nucleotide polymorphisms (SNPs) are located in non-coding regions of the human genome. Interestingly, SNPs in long non-coding RNAs (lncRNAs) may result in the disruption of their secondary structure, affecting their function, and in turn, the expression of potentially pathogenic pathways. In the present work, the function of a virus-induced T1D-associated lncRNA named ARGI (Antiviral Response Gene Inducer) is characterized. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic β cells and binds to CTCF to interact with the promoter and enhancer regions of IFNβ and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the T1D risk allele in ARGI induces a change in its secondary structure. Interestingly, the T1D risk genotype induces hyperactivation of type I IFN response in pancreatic β cells, an expression signature that is present in the pancreas of T1D patients. These data shed light on the molecular mechanisms by which T1D-related SNPs in lncRNAs influence pathogenesis at the pancreatic β cell level and opens the door for the development of therapeutic strategies based on lncRNA modulation to delay or avoid pancreatic β cell inflammation in T1D. ; SCOPUS: ar.j ; info:eu-repo/semantics/published
وصف الملف: 1 full-text file(s): application/pdf
العلاقة: uri/info:doi/10.1002/advs.202300063; uri/info:doi/10.1101/2022.12.01.518685; uri/info:pmid/37382191; uri/info:scp/85163786412; https://dipot.ulb.ac.be/dspace/bitstream/2013/359748/3/2022.12.01.518685.full.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/359748Test
-
2دورية أكاديمية
المؤلفون: Chauvin, Adrien, Bittencourt, Carla, Galais, Mathilde, Sauvage, Lionel, Bellefroid, Maxime, Van Lint, Carine, Op De Beeck, Anne, Snyders, Rony, Reniers, François
المصدر: Surface & coatings technology
مصطلحات موضوعية: Chimie des surfaces et des interfaces
الوصف: info:eu-repo/semantics/published
وصف الملف: 1 full-text file(s): application/pdf
العلاقة: https://dipot.ulb.ac.be/dspace/bitstream/2013/369867/3/1-s2.0-S0257897223007119-main.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/369867Test
-
3دورية أكاديمية
المؤلفون: Coomans de Brachène, Alexandra, Alvelos, Maria Ines, Szymczak, Florian, Zimath, Priscila L., Castela, Angela, Marmontel de Souza, Bianca, Roca Rivada, Arturo, Marín-Cañas, Sandra, Yi, Xiaoyan, Op de Beeck, Anne, Morgan, Noel G., Sonntag, Sebastian, Jawurek, Sayro, Title, Alexandra C., Yesildag, Burcak, Pattou, François, Kerr-Conte, Julie, Montanya, Eduard, Nacher, Montserrat, Marselli, Lorella
المصدر: Diabetologia; May2024, Vol. 67 Issue 5, p908-927, 20p
مستخلص: Aims/hypothesis: The proinflammatory cytokines IFN-α, IFN-γ, IL-1β and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, the specific role of each of these cytokines individually on pancreatic beta cells remains unknown. Methods: We used deep RNA-seq analysis, followed by extensive confirmation experiments based on reverse transcription-quantitative PCR (RT-qPCR), western blot, histology and use of siRNAs, to characterise the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by type 1 diabetes. Results: IFN-α and IFN-γ had a greater impact on the beta cell transcriptome when compared with IL-1β and TNF-α. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from individuals with type 1 diabetes, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to 'danger signals' such as viral infections. Zinc finger NFX1-type containing 1 (ZNFX1), a double-stranded RNA sensor, was identified as highly induced by IFNs and shown to play a key role in the antiviral response in beta cells. Conclusions/interpretation: These data suggest that IFN-α and IFN-γ are key cytokines at the islet level in human type 1 diabetes, contributing to the triggering and amplification of autoimmunity. [ABSTRACT FROM AUTHOR]
: Copyright of Diabetologia is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
-
4دورية أكاديمية
المؤلفون: Szymczak, Florian, Alvelos, Maria Inês, Marin Canas, Sandra, Oliveira Castela, Angela Sofia, Demine, Stéphane, Colli, Maikel Luis, Op De Beeck, Anne, Thomaidou, Sofia, Marselli, L., Zaldumbide, Arnaud AZ, Marchetti, Piero, Eizirik, Décio L
المصدر: Science advances, 8 (37
مصطلحات موضوعية: Biologie
الوصف: IFNα is a key regulator of the dialogue between pancreatic β cells and the immune system in early type 1 diabetes (T1D). IFNα up-regulates HLA class I expression in human β cells, fostering autoantigen presentation to the immune system. We observed by bulk and single-cell RNA sequencing that exposure of human induced pluripotent-derived islet-like cells to IFNα induces expression of HLA class I and of other genes involved in antigen presentation, including the transcriptional activator NLRC5. We next evaluated the global role of NLRC5 in human insulin-producing EndoC-βH1 and human islet cells by RNA sequencing and targeted gene/protein determination. NLRC5 regulates expression of HLA class I, antigen presentation–related genes, and chemokines. NLRC5 also mediates the effects of IFNα on alternative splicing, a generator of β cell neoantigens, suggesting that it is a central player of the effects of IFNα on β cells that contribute to trigger and amplify autoimmunity in T1D. ; SCOPUS: ar.j ; info:eu-repo/semantics/published
وصف الملف: 1 full-text file(s): application/pdf
العلاقة: uri/info:doi/10.1126/sciadv.abn5732; uri/info:pmid/36103539; uri/info:scp/85138448750; https://dipot.ulb.ac.be/dspace/bitstream/2013/352916/3/sciadv.abn5732-1.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/352916Test
-
5رسالة جامعية
المؤلفون: Op De Beeck, Anne
مرشدي الرسالة: Szpirer, Claude
مصطلحات موضوعية: Sciences exactes et naturelles
الوصف: Doctorat en Sciences
info:eu-repo/semantics/nonPublishedوصف الملف: 1 v.
-
6دورية أكاديمية
المؤلفون: Kteily, Karen, Pening, David, Diaz Vidal, Paula, Devos, Melody, Dechene, Julie, Op De Beeck, Anne, Botteaux, Anne, Janssens, Sandie, Van den Abbeel, E, Goldrat, Ornite, Delbaere, Anne, Demeestere, Isabelle
المصدر: Human reproduction
مصطلحات موضوعية: Gynécologie, Cancérologie, Sciences biomédicales
الوصف: Study question Can SARS-CoV-2 mRNA be detected in the reproductive tract of asymptomatic patients undergoing ART? Summary answer SARS-CoV-2 mRNA is not detectable in semen, follicular fluid, vaginal secretions or residual medulla from ovarian tissue cryopreservation procedures in asymptomatic patients who undergo ART, irrespective of the results of a triage questionnaire and a nasopharyngeal SARS-CoV-2 RNA detection test. What is known already The SARS-CoV-2 pandemic had a huge impact on the activities of fertility clinics. Although some studies reported the presence of SARS-CoV-2 mRNA in the reproductive system during or after acute COVID-19 symptomatic infections, uncertainties remain regarding the presence of viral mRNA in the reproductive material and follicular fluid of asymptomatic patients undergoing ART. Study design, size, duration An observational cohort trial of residual material samples including semen, follicular fluid, vaginal secretions and ovarian medulla was conducted during the second pandemic wave in Brussels, from September, 2020 to April, 2021. Participants/materials, setting, methods All patients who underwent ART (IIU, IVF/ICSI, oocyte and ovarian tissue cryopreservation) responded to a triage questionnaire at the beginning and end of the cycle and underwent nasopharyngeal swab collection for SARS-CoV-2 RNA detection by RT-PCR before the procedure according to standard recommendations. For semen analysis, only the questionnaire was requested the day before the sample collection. The ART cycles of patients with positive nasopharyngeal SARS-CoV-2 RNA detection tests and/or questionnaires were canceled except for those that could not be postponed. After providing informed consent, swabs on residual materials were collected the day of the oocyte, ovarian tissue or semen collection and were processed for RT-qPCR. Main results and the role of chance A total of 394 samples from 291 patients were analysed. Amongst them, 20 samples were obtained from patients with a positive questionnaire ...
وصف الملف: 1 full-text file(s): application/pdf
العلاقة: uri/info:doi/10.1093/humrep/deab255; uri/info:pmid/34741508; uri/info:scp/85123499029; https://dipot.ulb.ac.be/dspace/bitstream/2013/333914/3/deab255.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/333914Test
-
7دورية أكاديمية
المؤلفون: Coomans De Brachene, Alexandra, Castela, Angela, Op De Beeck, Anne, Mirmira, Raghavendra R.G., Marselli, Lorella, Marchetti, Piero, Masse, Craig, Miao, Wenyan, Leit, Silvana, Evans-Molina, Carmella, Eizirik, Decio L.
المصدر: Diabetes, obesity and metabolism
مصطلحات موضوعية: Sciences bio-médicales et agricoles
الوصف: Aim: Type 1 diabetes (T1D) is a chronic autoimmune disease leading to progressive loss of pancreatic beta cells. Interferon (IFN)-α plays a critical role in the crosstalk between pancreatic beta cells and the immune system in early insulitis. In human beta cells IFNα signals through JAK1 and TYK2, leading to endoplasmic reticulum stress, inflammation and HLA class I overexpression. IFNα, acting synergistically with IL-1β, induces apoptosis. Polymorphisms in TYK2 that decrease its activity are associated with protection against T1D, and we hypothesized that pharmacological inhibitors that specifically target TYK2 could protect human beta cells against the deleterious effects of IFNα. Materials and Methods: Two TYK2 inhibitors provided by Nimbus Lakshmi were tested in human insulin-producing EndoC-βH1 cells and human islets to evaluate their effect on IFNα signalling, beta-cell function and susceptibility to viral infection using RT-qPCR, western blot, immunofluorescence, ELISA and nuclear dyes. Results: The two TYK2 inhibitors tested prevented IFNα-induced human beta-cell gene expression in a dose-dependent manner. They also protected human islets against IFNα + IL-1β-induced apoptosis. Importantly, these inhibitors did not modify beta-cell function or their survival following infection with the potential diabetogenic coxsackieviruses CVB1 and CVB5. Conclusions: The two TYK2 inhibitors tested inhibit the IFNα signalling pathway in human beta cells, decreasing its pro-inflammatory and pro-apoptotic effects without sensitizing the cells to viral infection. The preclinical findings could pave the way for future clinical trials with TYK2 inhibitors for the prevention and treatment of type 1 diabetes. ; SCOPUS: ar.j ; info:eu-repo/semantics/published
وصف الملف: 1 full-text file(s): application/pdf
العلاقة: uri/info:doi/10.1111/dom.14104; uri/info:pmid/32476252; uri/info:scp/85087436986; https://dipot.ulb.ac.be/dspace/bitstream/2013/308093/3/dom.14104.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/308093Test
-
8دورية أكاديمية
المؤلفون: Colli, Maikel L., Hill, Jessica L. E., Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo S., Leete, Pia, Coomans de Brachène, Alexandra, Paula, Flavia M. M., Op de Beeck, Anne, Castela, Angela, Marselli, Lorella, Krogvold, Lars, Dahl-Jorgensen, Knut, Marchetti, Piero, Morgan, Noel G., Richardson, Sarah J., Eizirik, Décio L.
المساهمون: Colli, Maikel L., Hill, Jessica L. E., Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo S., Leete, Pia, Coomans de Brachène, Alexandra, Paula, Flavia M. M., Op de Beeck, Anne, Castela, Angela, Marselli, Lorella, Krogvold, Lar, Dahl-Jorgensen, Knut, Marchetti, Piero, Morgan, Noel G., Richardson, Sarah J., Eizirik, Décio L.
مصطلحات موضوعية: CD274, Immune checkpoint inhibitor, IRF1, Pancreatic beta cell, Pancreatic islet, PDL-1, PDL1, Type 1 diabete, Adolescent, Adult, B7-H1 Antigen, Biomarker, Cell Line, Child, Preschool, Diabetes Mellitus, Type 1, Human, Insulin-Secreting Cell, Interferon Regulatory Factor-1, Interferon-alpha, Interferon-gamma, Islets of Langerhan, Middle Aged, Young Adult, Gene Expression Regulation, Biochemistry, Genetics and Molecular Biology (all)
الوصف: Background: Antibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). It remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated. Methods: The expression of PDL1, IRF1, insulin and glucagon was evaluated in samples of T1D donors by immunofluorescence. Cytokine-induced PDL1 expression in the human beta cell line, EndoC-βH1, and in primary human pancreatic islets was determined by real-time RT-PCR, flow cytometry and Western blot. Specific and previously validated small interference RNAs were used to inhibit STAT1, STAT2, IRF1 and JAK1 signaling. Key results were validated using the JAK inhibitor Ruxolitinib. Findings: PDL1 was present in insulin-positive cells from twelve T1D individuals (6 living and 6 deceased donors) but absent from insulin-deficient islets or from the islets of six non-diabetic controls. Interferons-α and -γ, but not interleukin-1β, induced PDL1 expression in vitro in human islet cells and EndoC-βH1 cells. Silencing of STAT1 or STAT2 individually did not prevent interferon-α-induced PDL1, while blocking of JAKs – a proposed therapeutic strategy for T1D – or IRF1 prevented PDL1 induction. Interpretation: These findings indicate that PDL1 is expressed in beta cells from people with T1D, possibly to attenuate the autoimmune assault, and that it is induced by both type I and II interferons via IRF1.
وصف الملف: ELETTRONICO
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30269996; info:eu-repo/semantics/altIdentifier/wos/WOS:000447685300041; volume:36; firstpage:367; lastpage:375; numberofpages:9; journal:EBIOMEDICINE; info:eu-repo/grantAgreement/EC/H2020/115797 667191; http://hdl.handle.net/11568/954955Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85054193057; https://www.sciencedirect.com/science/article/pii/S2352396418303980Test
الإتاحة: https://doi.org/10.1016/j.ebiom.2018.09.040Test
http://hdl.handle.net/11568/954955Test
https://www.sciencedirect.com/science/article/pii/S2352396418303980Test -
9دورية أكاديمية
المؤلفون: Colli, Maikel Luis, Paula, Flavia M M, Marselli, Lorella, Marchetti, Piero, Roivainen, Merja, Eizirik, Decio L., Op De Beeck, Anne
المصدر: Journal of Innate Immunity
مصطلحات موضوعية: Sciences bio-médicales et agricoles, Endoplasmic reticulum stress, Enterovirus, IRE1α, Type 1 diabetes, c-Jun N-terminal kinase
الوصف: Type 1 diabetes (T1D) is an autoimmune disease characterized by islet inflammation and progressive pancreatic β cell destruction. The disease is triggered by a combination of genetic and environmental factors, but the mechanisms leading to the triggering of early innate and late adaptive immunity and consequent progressive pancreatic β cell death remain unclear. The insulin-producing β cells are active secretory cells and are thus particularly sensitive to endoplasmic reticulum (ER) stress. ER stress plays an important role in the pathologic pathway leading to autoimmunity, islet inflammation, and β cell death. We show here that group B coxsackievirus (CVB) infection, a putative causative factor for T1D, induces a partial ER stress in rat and human β cells. The activation of the PERK/ATF4/CHOP branch is blunted while the IRE1α branch leads to increased spliced XBP1 expression and c-Jun N-terminal kinase (JNK) activation. Interestingly, JNK1 activation is essential for CVB amplification in both human and rat β cells. Furthermore, a chemically induced ER stress preceding viral infection increases viral replication, in a process dependent on IRE1α activation. Our findings show that CVB tailors the unfolded protein response in β cells to support their replication, preferentially triggering the pro-viral IRE1α/XBP1s/JNK1 pathway while blocking the pro-apoptotic PERK/ATF4/CHOP pathway. ; SCOPUS: ar.j ; info:eu-repo/semantics/published
وصف الملف: 1 full-text file(s): application/pdf
العلاقة: uri/info:doi/10.1159/000496034; uri/info:pii/000496034; uri/info:pmid/30799417; uri/info:scp/85062057395; https://dipot.ulb.ac.be/dspace/bitstream/2013/284708/3/doi_268335.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/284708Test
-
10دورية أكاديمية
المؤلفون: Colli, Maikel L., Paula, Flavia M., Marselli, Lorella, Marchetti, Piero, Roivainen, Merja, Eizirik, Decio L., Op de beeck, Anne
المصدر: Journal of Innate Immunity ; volume 11, issue 4, page 375-390 ; ISSN 1662-811X 1662-8128
الوصف: Type 1 diabetes (T1D) is an autoimmune disease characterized by islet inflammation and progressive pancreatic β cell destruction. The disease is triggered by a combination of genetic and environmental factors, but the mechanisms leading to the triggering of early innate and late adaptive immunity and consequent progressive pancreatic β cell death remain unclear. The insulin-producing β cells are active secretory cells and are thus particularly sensitive to endoplasmic reticulum (ER) stress. ER stress plays an important role in the pathologic pathway leading to autoimmunity, islet inflammation, and β cell death. We show here that group B coxsackievirus (CVB) infection, a putative causative factor for T1D, induces a partial ER stress in rat and human β cells. The activation of the PERK/ATF4/CHOP branch is blunted while the IRE1α branch leads to increased spliced XBP1 expression and c-Jun N-terminal kinase (JNK) activation. Interestingly, JNK1 activation is essential for CVB amplification in both human and rat β cells. Furthermore, a chemically induced ER stress preceding viral infection increases viral replication, in a process dependent on IRE1α activation. Our findings show that CVB tailors the unfolded protein response in β cells to support their replication, preferentially triggering the pro-viral IRE1α/XBP1s/JNK1 pathway while blocking the pro-apoptotic PERK/ATF4/CHOP pathway.
