A5073776375- Diabetes and associated disorders
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Diet, Metabolism, and Disease
- Diabetes Management and Research
- Bacteriophages and microbial interactions
- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- RNA Research and Splicing
- Museums and Cultural Heritage
- Diverse academic and cultural studies
- RNA regulation and disease
- Microbial infections and disease research
- Ubiquitin and proteasome pathways
- Atherosclerosis and Cardiovascular Diseases
- Cultural Industries and Urban Development
- RNA modifications and cancer
Leiden University Medical Center
2018-2024
Indianapolis Zoo
2023
Readily accessible human pancreatic beta cells that are functionally close to primary adult a crucial model better understand cell physiology and develop new treatments for diabetes. We here report the characterization of EndoC-βH5 cells, latest in EndoC-βH family.EndoC-βH5 were generated by integrative gene transfer immortalizing transgenes hTERT SV40 large T along with Herpes Simplex Virus-1 thymidine kinase into fetal pancreas. Immortalizing removed after amplification using CRE...
The signal peptide of preproinsulin is a major source for HLA class I autoantigen epitopes implicated in CD8 T cell (CTL)–mediated β-cell destruction type 1 diabetes (T1D). Among them, the 10-mer epitope located at C-terminal end was found to be most prevalent patients with recent-onset T1D. While combined action peptidase and endoplasmic reticulum (ER) aminopeptidase (ERAP1) required processing peptide, mechanisms controlling trimming contribution T1D inflammatory milieu on these are...
IFNα is a key regulator of the dialogue between pancreatic β cells and immune system in early type 1 diabetes (T1D). up-regulates HLA class I expression human cells, fostering autoantigen presentation to system. We observed by bulk single-cell RNA sequencing that exposure induced pluripotent-derived islet-like induces other genes involved antigen presentation, including transcriptional activator NLRC5. next evaluated global role NLRC5 insulin-producing EndoC-βH1 islet targeted gene/protein...
Abstract Aims/hypothesis The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction type 1 diabetes. Here, we studied the role early innate cytokines (IFNα) late immune adaptive events (IFNɣ) insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells. Methods Single-cell transcriptomics human pancreatic islets was used study composition (immuno)proteasome....
Introduction Enterovirus infection has long been suspected as a possible trigger for type 1 diabetes. Upon infection, viral double-stranded RNA (dsRNA) is recognized by membrane and cytosolic sensors that orchestrate I interferon signaling the recruitment of innate immune cells to pancreatic islets. In this context, adenosine deaminase acting on (ADAR1) editing plays an important role in dampening response inducing mispairing, destabilizing duplexes thus preventing excessive activation....
Tyrosine protein-kinase 2 (TYK2), a member of the Janus kinase family, mediates inflammatory signaling through multiple cytokines, including interferon-α (IFNα), interleukin (IL)-12, and IL-23. Missense mutations in TYK2 are associated with protection against type 1 diabetes (T1D), inhibition shows promise management other autoimmune conditions. Here, we evaluated effects specific inhibitors (TYK2is) pre-clinical models T1D. First, human β cells, cadaveric donor islets, iPSC-derived islets...
Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell–mediated destruction of the insulin-producing pancreatic β-cells. Increasing evidence suggest that β-cells themselves contribute to their own generating neoantigens through production aberrant or modified proteins escape central tolerance. We recently demonstrated ribosomal infidelity amplified stress could lead generation in human β-cells, emphasizing participation nonconventional translation events...
Abstract Aims/hypothesis Transcriptome analyses revealed insulin-gene-derived transcripts in non-beta endocrine islet cells. We studied alternative splicing of human INS mRNA pancreatic islets. Methods Alternative insulin pre-mRNA was determined by PCR analysis performed on RNA and single-cell RNA-seq analysis. Antisera were generated to detect variants tissue using immunohistochemistry, electron microscopy western blot confirm the expression variants. Cytotoxic T lymphocyte (CTL) activation...
Interferon-α (IFNα) plays a prominent role in type 1 diabetes (T1D) pathogenesis and mediates its effects through the IFN receptor (IFNAR) protein tyrosine kinases JAK1 TYK2. Polymorphisms that decrease TYK2 activity are protective against T1D, inhibitors (TYKi) being evaluated for therapeutic benefit other autoimmune conditions. To test whether BMS-986202 BMS-986165 have similar efficacy diverse models of we their effect vitro on human islets, EndoC-βH1 cells, iPSC-derived islet-like...
Over the last few years, there has been an increasing interest on part of cultural institutions to develop a series educational activities and initiatives. Informal arts education this kind serves as dissemination great potential for attracting wider audience museums institutions, enhancing user experience. It is also practice that increases participation innovation in learning societal level. Apart from in-house events activities, have moved into digital realm, using affordances new...
Type 1 diabetes is an autoimmune disease characterized by autoreactive T-cell mediated destruction of the insulin-producing pancreatic beta-cells. Increasing evidence suggest that beta-cells themselves contribute to their own generating neo-antigens through production aberrant or modified proteins escape central tolerance. We have recently demonstrated ribosomal infidelity amplified stress could lead generation neoantigens in human beta-cells, emphasizing participation nonconventional...
Type 1 diabetes is an autoimmune disease characterized by autoreactive T-cell mediated destruction of the insulin-producing pancreatic beta-cells. Increasing evidence suggest that beta-cells themselves contribute to their own generating neo-antigens through production aberrant or modified proteins escape central tolerance. We have recently demonstrated ribosomal infidelity amplified stress could lead generation neoantigens in human beta-cells, emphasizing participation nonconventional...