المؤلفون: Chaffey, Jessica R., Young, Jay, Leslie, Kaiyven A., Partridge, Katie, Akhbari, Pouria, Dhayal, Shalinee, Hill, Jessica L., Wedgwood, Kyle C. A., Burnett, Edward, Russell, Mark A., Richardson, Sarah J., Morgan, Noel G.

المساهمون: Diabetes UK, Juvenile Diabetes Research Foundation International, Medical Research Council

المصدر: Scientific Reports ; volume 11, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: The generation of a human pancreatic beta cell line which reproduces the responses seen in primary beta cells, but is amenable to propagation in culture, has long been an important goal in diabetes research. This is particularly true for studies focussing on the role of enteroviral infection as a potential cause of beta-cell autoimmunity in type 1 diabetes. In the present work we made use of a clonal beta cell line (1.1B4) available from the European Collection of Authenticated Cell Cultures, which had been generated by the fusion of primary human beta-cells with a pancreatic ductal carcinoma cell, PANC-1. Our goal was to study the factors allowing the development and persistence of a chronic enteroviral infection in human beta-cells. Since PANC-1 cells have been reported to support persistent enteroviral infection, the hybrid 1.1B4 cells appeared to offer an ideal vehicle for our studies. In support of this, infection of the cells with a Coxsackie virus isolated originally from the pancreas of a child with type 1 diabetes, CVB4.E2, at a low multiplicity of infection, resulted in the development of a state of persistent infection. Investigation of the molecular mechanisms suggested that this response was facilitated by a number of unexpected outcomes including an apparent failure of the cells to up-regulate certain anti-viral response gene products in response to interferons. However, more detailed exploration revealed that this lack of response was restricted to molecular targets that were either activated by, or detected with, human-selective reagents. By contrast, and to our surprise, the cells were much more responsive to rodent-selective reagents. Using multiple approaches, we then established that populations of 1.1B4 cells are not homogeneous but that they contain a mixture of rodent and human cells. This was true both of our own cell stocks and those held by the European Collection of Authenticated Cell Cultures. In view of this unexpected finding, we developed a strategy to harvest, isolate and ...

الإتاحة: https://doi.org/10.1038/s41598-021-94878-yTest
https://www.nature.com/articles/s41598-021-94878-y.pdfTest
https://www.nature.com/articles/s41598-021-94878-yTest

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

المؤلفون: Colli, Maikel Luis, Hill, Jessica L E, Marroquí, Laura, Chaffey, Jessica, Dos Santos, Reinaldo Sousa, Leete, Pia, Coomans De Brachene, 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, Decio L.

المصدر: EBioMedicine, 36

مصطلحات موضوعية: Sciences bio-médicales et agricoles, CD274, IRF1, Immune checkpoint inhibitor, PDL-1, PDL1, Pancreatic beta cells, Pancreatic islets, Type 1 diabetes

الوصف: 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. ; “Innovative Medicines Initiative 2”;“European Union(EU)”“Horizon2020”; and EFPIA”,“JDRF International” and The Leona M.and Harry B.Helmsley Charitable Trust”; ; SCOPUS: ar.j ; info:eu-repo/semantics/published

وصف الملف: 2 full-text file(s): application/pdf | application/pdf

العلاقة: uri/info:doi/10.1016/j.ebiom.2018.09.040; uri/info:pii/S2352-3964(18)30398-0; uri/info:pmid/30269996; uri/info:scp/85054193057; uri/info:bibcode/innodia; uri/info:sici/30269996; https://dipot.ulb.ac.be/dspace/bitstream/2013/277638/5/main.pdfTest; https://dipot.ulb.ac.be/dspace/bitstream/2013/277638/6/doi_261265.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/277638Test

الإتاحة: http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/277638Test
https://dipot.ulb.ac.be/dspace/bitstream/2013/277638/5/main.pdfTest