A5055750637- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Vascular Malformations Diagnosis and Treatment
- Systemic Lupus Erythematosus Research
- Immunotherapy and Immune Responses
- Intracranial Aneurysms: Treatment and Complications
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Intracerebral and Subarachnoid Hemorrhage Research
- Bone Metabolism and Diseases
- Hereditary Neurological Disorders
- Genetic Associations and Epidemiology
- Immune cells in cancer
- Metaheuristic Optimization Algorithms Research
- Viral Infections and Immunology Research
- Myofascial pain diagnosis and treatment
- Rheumatoid Arthritis Research and Therapies
- interferon and immune responses
- Evolutionary Algorithms and Applications
- Pharmacological Effects of Natural Compounds
- Genetic and phenotypic traits in livestock
- HER2/EGFR in Cancer Research
- Genetic Mapping and Diversity in Plants and Animals
Uppsala University
2021-2022
Karolinska Institutet
2014-2020
Centre for Human Genetics
2016
Background To facilitate the development of therapies for rheumatoid arthritis (RA), Innovative Medicines Initiative BTCure has combined experience from several laboratories worldwide to establish a series protocols different animal models that reflect pathogenesis RA. Here, we describe chronic pristane-induced (PIA) model in DA rats, and provide detailed instructions set up evaluate reporting data. Methods We optimized dose pristane immunization procedures determined effect age, gender,...
Background and Purpose: Cerebral cavernous malformations (CCM) present as mulberry-like of the microvasculature central nervous system. Current medical treatment CCM lesions is limited to surgical removal vascular malformations. It is, therefore, important identify therapeutic drug treatments for patients with CCM. Propranolol has shown great benefit in infantile hemangioma. In addition, who receive propranolol have demonstrated a reduction their lesions. Our investigation set out provide...
Cerebral Cavernous Malformation (CCM) is a brain vascular disease with various neurological symptoms. In this study, we describe the inflammatory profile in CCM and show for first time formation of neutrophil extracellular traps (NETs) rodents humans CCM. Through RNA-seq analysis cerebellum endothelial cells from wild-type mice an cell-specific ablation Ccm3 gene (Ccm3iECKO), that Ccm3iECKO have increased expression inflammation-related genes. These genes encode proinflammatory cytokines...
Inducible nitric oxide from skin macrophages promotes IL-17 release and psoriatic arthritis by innate lymphoid cells.
Cerebral cavernous malformation (CCM) is a neurovascular disease that results in various neurological symptoms. Thrombi have been reported surgically resected CCM patient biopsies, but the molecular signatures of these thrombi remain elusive. Here, we investigated kinetics formation and how affect vasculature contribute to cerebral hypoxia. We used RNA sequencing investigate transcriptome mouse brain endothelial cells with an inducible endothelial-specific Ccm3 knock-out (Ccm3-iECKO). found...
Abstract Rheumatoid arthritis (RA) is associated with amino acid variants in multiple MHC molecules. The association to class II (MHC-II) has been studied several animal models of RA. In most cases these depend on T cells restricted a single immunodominant peptide the immunizing Ag, which does not resemble autoreactive An exception pristane-induced (PIA) rat where polyclonal induce chronic after being primed against endogenous Ags. this study, we used mixed genetic and functional approach...
Endogenous nucleic acids and their receptors may be involved in the initiation of systemic autoimmune diseases including rheumatoid arthritis (RA). As role DNA sensing Toll-like receptor (TLR) 9 RA is unclear, we aimed to investigate its involvement pathogenesis using three different experimental models RA. The data obtained revealed TLR9 T cell-dependent phase inflammatory arthritis. In rats with pristane-induced (PIA), inhibition before disease onset reduced significantly almost completely...
Significance The role of the MHC region has been a long-standing issue in chronic inflammatory diseases, such as rheumatoid arthritis, and it not possible to identify underlying specific polymorphism. Here, we provide evidence that some association must be explained by how closely linked genes operate together haplotype blocks. We identified conserved haplotype, Ltab-Ncr3, comprising five ( lymphotoxin α β, Tnf , leukocyte-specific transcript 1 natural cytotoxicity-triggering receptor 3 )...
Genetic variation in the major histocompatibility complex (MHC) affects CD4∶CD8 lineage commitment and MHC expression. However, contribution of specific genes this gene-dense region has not yet been resolved. Nor it established whether same regulate expression T cell selection. Here, we assessed impact natural genetic on using two models rat. First, mapped Quantitative Trait Loci (QTLs) associated with class I II protein ratio outbred Heterogeneous Stock rats. We identified 10 QTLs across...
Mineral oils are extensively used in our daily life, food, cosmetics, biomedicine, vaccines and different industrial applications. However, exposure to these mineral has been associated with immune adjuvant effects the development of autoimmune diseases. Here we investigate structural impacts hydrocarbon oil molecules on their adjuvanticity autoimmunity. First, showed that small atomic differences could result experimental arthritis DA rats differing disease severity, incidence, weight...
Aims: In this study, we investigate the role of reactive oxygen species (ROS) and nitrogen (RNS) in autoimmune diseases. We focus on oxidative regulation at interaction between antigen-presenting cells (APCs) T cells, consequent effect ROS RNS type II collagen (CII)-induced arthritis (CIA) model mice. Results: Mice deficient peroxide, due to a mutation Ncf1 gene, develop an exaggerated CIA stronger cell response CII. contrast, nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester...
Abstract Objective Chronic inflammation of the peripheral joints is a hallmark rheumatoid arthritis (RA). The autoantibody response in RA has been shown to be directed mainly ubiquitous antigens, whereas cartilage proteins less extensively investigated. This study was undertaken characterize immune pristane‐induced (PIA) rat cartilage‐specific type II collagen (CII) and XI (CXI) genetically fine‐map their underlying major histocompatibility complex (MHC) associations. Methods genetic control...
Collagen XI (CXI) is a heterotrimeric molecule with triple helical structure in which the α3(XI) chain identical to α1(II) of collagen II (CII), but extensive posttranslational modifications. CXI molecules are intermingled cartilage fibers, mainly composed CII. One alpha chains shared CII and contains immunodominant T cell epitope, it unclear whether there B epitopes as antibodies tend recognize structures.Mice expressing susceptible immune response gene Aq were immunized or CXI. Serum...
Abstract To test the impact of genetic heterogeneity on cis- and trans-mediated mechanisms gene expression regulation, we profiled transcriptome adipose tissue in 20 inbred congenic strains derived from diabetic Goto–Kakizaki (GK) rats Brown–Norway (BN) controls, which contain well-defined blocks (1–183 Mb) polymorphisms, 123 genetically heterogeneous an (GK × BN)F2 offspring. Within each identified 73–1351 differentially expressed genes (DEGs), only 7.7% mapped within blocks, may be...
Abstract Background Increasing evidence has suggested that a single nucleotide polymorphism in the Ncf1 gene is associated with experimental autoimmune encephalomyelitis (EAE). However, mechanisms of NCF1-induced immunoregulatory effects remain poorly understood. In this study, we focus on NCF1 deficiency-mediated EAE NOS2 dependent and independent ways. Methods To determine during development, have established recombinant mouse strains deficient at and/or crossbreeding system. Different...
Antigen presentation by the MHC-II to CD4+ T cells is important in adaptive immune responses. The class II transactivator (CIITA human and C2TA mouse) master regulator of gene expression. It coordinates transcription factors necessary for molecules. In humans, genetic variations CIITA have been associated with differential expression susceptibility autoimmune diseases. Here we made use a C2ta congenic mouse strain (expressing haplotype H-2q ) investigate effect natural polymorphisms type I...