- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- Renal Transplantation Outcomes and Treatments
- Psoriasis: Treatment and Pathogenesis
- Monoclonal and Polyclonal Antibodies Research
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Dermatology and Skin Diseases
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Endometriosis Research and Treatment
- Renal Diseases and Glomerulopathies
- Pregnancy and Medication Impact
- Pregnancy and preeclampsia studies
- Organ Transplantation Techniques and Outcomes
- Immunodeficiency and Autoimmune Disorders
- Complement system in diseases
- T-cell and Retrovirus Studies
- Multiple Myeloma Research and Treatments
- Reproductive Physiology in Livestock
- Diabetes and associated disorders
- Microbial infections and disease research
- Cancer Immunotherapy and Biomarkers
Radboud University Nijmegen
2015-2024
Radboud University Medical Center
2015-2024
Radboud Institute for Molecular Life Sciences
2012-2023
University Medical Center
2021
Laboratory of Molecular Genetics
2010-2020
Utrecht University
1988-2014
Erasmus MC
2004-2014
Nijmegen Institute for Scientist Practitioners in Addiction
2011-2013
Institute of Infection and Immunity
2011-2013
Dutch Blood Transfusion Society
1997-2009
Topical application of coal tar is one the oldest therapies for atopic dermatitis (AD), a T helper 2 (Th2) lymphocyte–mediated skin disease associated with loss-of-function mutations in barrier gene, filaggrin (FLG). Despite its longstanding clinical use and efficacy, molecular mechanism therapy unknown. Using organotypic models primary keratinocytes from AD patients controls, we found that activated aryl hydrocarbon receptor (AHR), resulting induction epidermal differentiation. AHR...
Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct those generated at the plasma membrane. The activity of natural killer (NK) cells, are important effectors innate immunity and regulators adaptive immunity, controlled primarily that cell surface. Here we show cytokine secretion resting human NK cells induced soluble, but not solid-phase, antibodies to immunoglobulin-like receptor (KIR) 2DL4, for leukocyte antigen (HLA)-G....
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immunity. Recent studies have revealed that the immunity is associated with bias toward granulopoiesis bone marrow hematopoietic progenitor but it unknown whether BCG vaccination also leads to functional reprogramming mature neutrophils. Here, we show healthy...
Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate activation and memory that indicative immunity. We established personal profiles chromatin accessibility maps over a 90-day time course BCG vaccination in 323 Our...
A single dose of the anti-CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not secondary lymphoid organs. Modulation this remaining population due to treatment may contribute therapeutic effects rituximab. To assess vivo we used lymph nodes (LNs) collected during renal transplant surgery patients who had received 4 weeks earlier preparation for an ABO-incompatible transplantation. Rituximab resulted lower percentage naïve (IgD(+)CD27(-))...
The success of immunotherapy with dendritic cells (DC) to treat cancer is dependent on effective migration the lymph nodes and subsequent activation antigen-specific T cells. In this study, we investigated fate DC after intradermal (i.d.) or intranodal (i.n.) administration consequences for immune activating potential vaccines in melanoma patients.DC were i.d. i.n. administered 25 patients metastatic scheduled regional node resection. To track vivo scintigraphic imaging by...
The immune modulating capacity of vitamin D(3) is well-recognized. Ultra-violet (UV) exposure determines production in vivo and varies through the course year, especially temperate regions. However, it not known whether human innate response differs due to seasonality. To validate seasonal effects , effect 1,25(OH)(2) on peripheral blood mononuclear cells (PBMC) cytokine was first determined vitro. decreased interleukin (IL)-6 tumour necrosis factor (TNF)-α release by PBMC stimulated with...
Immunotherapy based on natural killer (NK) cell infusions is a potential adjuvant treatment for many cancers. Such therapeutic application in humans requires large numbers of functional NK cells that have been selected and expanded using clinical grade protocols. We established an extremely efficient cytokine-based culture system ex vivo expansion from hematopoietic stem progenitor umbilical cord blood (UCB). Systematic refinement this two-step novel medium resulted therapeutically...
We evaluated the efficacy and safety of rituximab as induction therapy in renal transplant patients. In a double-blind, placebo-controlled study, 280 adult patients were randomized between single dose (375 mg/m(2)) or placebo during surgery. Patients stratified according to panel-reactive antibody (PRA) value rank number transplantation. Maintenance immunosuppression consisted tacrolimus, mycophenolate mofetil steroids. The primary endpoint was incidence biopsy proven acute rejection (BPAR)...
Severe burn injury causes local and systemic immune responses that can persist up to months, lead inflammatory response syndrome, organ damage long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed temporal peripheral blood profile 20 wound patients admitted intensive care by flow cytometry secretome profiling, compared data from healthy subjects. The...
Treg based immunotherapy is of great interest to facilitate tolerance in autoimmunity and transplantation. For clinical trials, it essential have a grade isolation protocol accordance with Good Manufacturing Practice (GMP) guidelines. To obtain sufficient for immunotherapy, subsequent ex vivo expansion might be needed.Treg were isolated from leukapheresis products by CliniMACS GMP strategies, using anti-CD25, anti-CD8 anti-CD19 coated microbeads. procedures led 40-60% pure...
Mycophenolic acid is the active ingredient of immunosuppressant mycophenolate mofetil that widely used in transplantation medicine and autoimmunity. inhibits inosine monophosphate dehydrogenase, an enzyme involved biosynthesis guanine nucleotides required for lymphocyte clonal expansion. Here, we present novel insights into mechanisms underlying mycophenolic acid-mediated suppression human CD4+ T cells. Upon CD3/CD28 stimulation, inhibited cell IL-17, IFN-γ TNF-α production but not IL-2...
Is menstrual blood a suitable source of endometrial derived lymphocytes?Mononuclear cells isolated from samples (menstrual mononuclear (MMC)) are clearly distinct peripheral (PBMC) and show strong resemblance with biopsy-derived cells.A critical event in the onset pregnancy is implantation embryo uterine wall. The immune cell composition endometrium at time considered pivotal for success. Despite advancing knowledge on population uterus, role reproductive disorders still not fully resolved,...