A5049274302- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Vitamin D Research Studies
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- Ubiquitin and proteasome pathways
- Animal Virus Infections Studies
- Vitamin C and Antioxidants Research
- CAR-T cell therapy research
- Per- and polyfluoroalkyl substances research
- Contact Dermatitis and Allergies
- Adrenal Hormones and Disorders
- Cytokine Signaling Pathways and Interactions
- Microbial infections and disease research
- Immune cells in cancer
- Fluoride Effects and Removal
- Ethics in Clinical Research
- T-cell and Retrovirus Studies
- Cellular Mechanics and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Genetics and Neurodevelopmental Disorders
- Respiratory viral infections research
- BRCA gene mutations in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
Statens Serum Institut
2020-2024
Danmarks Nationalbank
2021-2023
LEO Foundation
2021
University of Copenhagen
2006-2021
Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic may contribute an association with severity. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30–70 years known SARS-CoV-2 infection. PFAS concentrations measured at background exposures included five PFASs immunotoxic. Register data was classify status, other...
the observed decrease in population neutralizing antibody titers corresponds to vaccine efficacy against polymerase chain reaction-confirmed Omicron infection Denmark and symptomatic United Kingdom. 3,4Taken together, vaccine-induced protective responses following a second third dose of BNT162b2 are transient additional booster doses may be necessary, particularly older people; however, conserved T-cell immunity nonneutralizing antibodies still provide protection hospitalization death.
The active form of vitamin D3, 1,25(OH)2D3, has significant immunomodulatory properties and is an important determinant in the differentiation CD4+ effector T cells. biological actions 1,25(OH)2D3 are mediated by D receptor (VDR) believed to correlate with VDR protein expression level a given cell. aim this study was determine if how itself regulates human We found that activated cells have capacity convert inactive 25(OH)D3 subsequently up-regulates approximately 2-fold. does not increase...
Abstract We explored the association between COVID-19 severity and vitamin D status using information from Danish nation-wide health registers, surveillance database stored blood samples national biobank. 25-hydroxyvitamin (25(OH)D) was measured tandem mass spectroscopy. The 25(OH)D levels severity, classified hierarchical as non-hospitalized, hospitalized but not admitted to an intensive care unit (ICU), ICU, death, evaluated by proportional odds ratios (POR) assuming proportionality four...
Abstract It is well known that protein kinase C (PKC) plays an important role in regulation of TCR cell surface expression levels. However, eight different PKC isotypes are present T cells, and to date the particular isotype(s) involved down-regulation remains be identified. The aim this study was identify elucidate mechanism by which they induce down-regulation. To accomplish this, we studied human line Jurkat, primary or mouse DO11.10 either overexpressed constitutive active...
Virus neutralization assays provide a means to quantitate functional antibody responses that block virus infection. These are instrumental in defining vaccine and therapeutic potency, immune evasion by viral variants, post-infection immunity. Here we describe the development, optimization evaluation of live microneutralization assay specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this assay, SARS-CoV-2 clinical isolates pre-incubated with serial diluted added...
Perturbation in JAK-STAT signaling has been reported the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with intra-cytoplasmic part IL-2Rγc located plasma membrane hematopoietic cells. Here we demonstrate that also ectopically expressed nucleus malignant We detected nuclear various CTCL lines and primary cells from patients Sézary syndrome, a leukemic variant CTCL. Nuclear localization was independent its kinase activity whereas STAT3 had modest effect on...
Abstract Background The course of coronavirus disease 2019 (COVID-19) seems to be aggravated by air pollution, and some industrial chemicals, such as the perfluorinated alkylate substances (PFASs), are immunotoxic may contribute well. Methods From Danish biobanks, we obtained plasma samples from 323 subjects aged 30-70 years with known SARS-CoV-2 infection. PFAS concentrations measured at background exposures included five PFASs immunotoxic. Register data was classify status, other health...
Several factors may account for the recent increased spread of SARS-CoV-2 Delta sub-lineage AY.4.2 in United Kingdom, Romania, Poland, and Denmark. We evaluated sensitivity to neutralisation by sera from 30 Comirnaty (BNT162b2 mRNA) vaccine recipients Denmark November 2021. was comparable other circulating lineages or sub-lineages. Conversely, less prevalent B.1.617.2 with E484K showed a significant more than 4-fold reduction that warrants surveillance strains acquired mutation.
Background: The different role of various immunological effector cells in contact hypersensitivity (CHS) is receiving increased attention. During the past decade, involvement cell types CHS has been investigated by use antibody‐induced depletion specific subtypes and studying knockout mice lacking one or more these populations. Objectives: To develop a method for collective cellular dynamics immune draining lymph nodes during intact animals. Patients/Methods: Mice were sensitized and/or...
Midline 1 (MID1) is a microtubule‐associated ubiquitin ligase that regulates protein phosphatase 2A activity. Loss‐of‐function mutations in MID1 lead to the X‐linked Opitz G/BBB syndrome characterized by defective midline development during embryogenesis. Here, we show strongly upregulated murine cytotoxic lymphocytes (CTLs), and it controls TCR signaling, centrosome trafficking, exocytosis of lytic granules. In accordance, find killing capacity −/− CTLs impaired. Transfection into...
Factors influencing SARS-CoV-2 antibody dynamics, transmission, waning and long COVID-19 symptomatology are still not fully understood.In the Danish section of Novo Nordisk Group, we performed a prospective seroepidemiological study during first second waves pandemic. All employees their household members (>18 years) were invited to participate in baseline (June-August 2020), 6-month follow-up (December 2020-January 2021), 12-month (August 2021) sampling. In total, 18,614 accepted provided...
Abstract The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the of physiological T cell responses. In this study, we show that expansion numbers virus-specific CD8+ cells impaired mice with mutated motif. mutation did not impair early signaling, nor it compromise recruitment or proliferation cells, but increased apoptosis rate activated by increasing down-regulation antiapoptotic molecule Bcl-2. This resulted 2-fold reduction...
PKC-θ plays a central role in TCR-induced IL-2 production and T-cell proliferation. The aim of the present study was to analyse how is regulated human T cells during activation differentiation. We show that found high-molecular disulfide-linked complex naïve cells, most likely inactive this form. In parallel with accumulation major redox regulators, glutathione thioredoxin, gradually reduced 82 kDa active form activation. demonstrate recruited plasma membrane dependent requires de novo...
Abstract TCR and cytokine receptor signaling play key roles in the complex homeostatic mechanisms that maintain a relative stable number of T cells throughout life. Despite mechanisms, slow decline naive is typically observed with age. The CD3γ di-leucine-based motif controls down-regulation plays central role fine-tuning expression cells. In this study, we show age-associated strongly accelerated CD3γLLAA knock-in mice homozygous for double leucine to alanine mutation motif, whereas memory...
Cytotoxic T (Tc) cells play a key role in the defense against virus infections. Tc recognize infected via T-cell receptor (TCR) and subsequently kill target by one or more cytotoxic mechanisms. Induction of mechanisms is finely tuned activation signals from TCR. To determine whether TCR down-regulation affects cytotoxicity cells, we studied down-regulation-deficient CD3γLLAA mice. We found that mice have reduced due to specific deficiency exocytosis lytic granules. this defect was reflected...
Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown strongly up-regulated murine cytotoxic T lymphocytes (CTLs), and it has significant impact on exocytosis of lytic granules killing capacity CTLs. The aims present study were determine localization migrating...
Abstract Several factors may account for the recent increased spread of SARS-CoV-2 Delta sublineage AY.4.2 in United Kingdom, Romania, Poland, and Denmark. Here, we evaluate sensitivity to neutralisation by sera from Pfizer/BioNTech (BNT162b2) vaccine recipients. was comparable other circulating lineages or sublineages. In contrast, more rare B.1.617.2+E484K variant showed a significant >4-fold reduction that warrants surveillance strains with acquired E484K mutation.
We have recently shown that the E3 ubiquitin ligase midline 1 ( MID 1) is upregulated in murine cytotoxic lymphocytes CTL ), where it controls exocytosis of lytic granules and killing capacity. Accordingly, from knock‐out −/− ) mice a 25–30% reduction cytotoxicity compared to wild‐type WT mice. wondered why gene did not affect more severely speculated whether 2, close homologue 1, might partially compensate for loss . Here, we showed like activated T cells. Furthermore, 2 two–twenty‐fold...
Abstract The CD3γ di-leucine-based (diL) receptor-sorting motif plays a central role in TCR down-regulation and clonal expansion of virus-specific T cells. However, the diL T-cell development is not known. In this study, we show that protein kinase C-induced abolished thymocytes from CD3γLLAA mice with mutated motif, have reduced numbers compared aged-matched wild-type mice. We found early thymocyte at β-selection checkpoint impaired resulting double negative (DN) 4 cells This was caused by...
The host genetics of SARS-CoV-2 has previously been studied based on cases from the earlier waves pandemic in 2020 and 2021, identifying 51 genomic loci associated with infection and/or severity. shown rapid sequence evolution increasing transmissibility, particularly for Omicron variants, which raises question whether this affected genetic factors. We performed a genome-wide association study variants including more than 150,000 four cohorts. identified 13 significant loci, only five were...
Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown strongly up-regulated murine cytotoxic T lymphocytes (CTLs), and it has significant impact on exocytosis of lytic granules killing capacity CTLs. The aims present study were determine localization migrating...