A5088639331- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Autoimmune and Inflammatory Disorders Research
- Cell Adhesion Molecules Research
- Blood disorders and treatments
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Mitochondrial Function and Pathology
- Cellular Mechanics and Interactions
- Lipid Membrane Structure and Behavior
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Hematopoietic Stem Cell Transplantation
- ATP Synthase and ATPases Research
- T-cell and Retrovirus Studies
- Advanced Electron Microscopy Techniques and Applications
- Carbon and Quantum Dots Applications
- Neuroscience and Neuropharmacology Research
- Nanoparticle-Based Drug Delivery
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- Electrochemical sensors and biosensors
- Cellular transport and secretion
- Immune cells in cancer
KTH Royal Institute of Technology
2023-2024
Karolinska Institutet
2020-2023
Science for Life Laboratory
2023
Swedish Orphan Biovitrum (United States)
2021
National Heart Lung and Blood Institute
2018
National Institutes of Health
2018
University of Manchester
2017-2018
Centre for Inflammation Research
2017-2018
Natural Killer (NK) cells can engage multiple virally infected or tumor sequentially and deliver perforin for cytolytic killing of these targets. Using microscopy to visualize degranulation from individual NK cells, we found that repeated activation via the Fc receptor CD16 decreased amount secreted. However, secretion was restored upon subsequent a different activating receptor, NKG2D. Repeated stimulation NKG2D also secretion, but this not rescued by CD16. These outcomes sequential could...
Natural killer (NK) cells are innate immune effectors that lyse virally infected and tumorigenic through the formation of an immunological synapse. Actin remodeling at lytic synapse is a critical requirement for multiple facets cytotoxic function. Activating receptor integrin signaling leads to regulated turnover actin, which required adhesion, sustained signaling, ultimately exocytosis. NK undergo granule exocytosis in hypodense regions pervasive actin network. Although these requirements...
An emerging new paradigm is that immune cell activation controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals activate or desensitize NK cells are, however, individual molecules do not replicate this nanoscale organization proteins. Here, we use graphene oxide (NGO) as a template to generate soluble clusters Natural Killer cell-activating antibodies. We control nanocluster size molecular number mimic...
Natural killer (NK) cells recognize virally infected and tumors. NK cell function depends on balanced signaling from activating receptors, recognizing products tumors or viruses, inhibitory receptors (such as KIR/Ly49), which major histocompatibility complex class I (MHC-I) molecules. KIR/Ly49 preserves tolerance to self but also conveys reactivity toward MHC-I–low target in a process known education. Here, we found that education were determined by the subcellular localization of tyrosine...
Membrane contact sites (MCSs) are hubs allowing various cell organelles to coordinate their activities. The dynamic nature of these and small size hinder analysis by current imaging techniques. To overcome limitations, we here design a series reversible chemogenetic reporters incorporating improved, low-affinity variants splitFAST, study the dynamics different MCSs at high spatiotemporal resolution, both in vitro vivo. We demonstrate that versatile suit experimental setups well, one address...
Chediak-Higashi syndrome (CHS) is a rare disorder caused by biallelic mutations in the lysosomal trafficking regulator gene (LYST), resulting formation of giant lysosomes or lysosome-related organelles several cell types. The disease characterized immunodeficiency and fatal hemophagocytic lymphohistiocytosis impaired function cytotoxic lymphocytes, including natural killer (NK) cells.We sought to determine underlying biochemical cause cytotoxicity NK cells patients with CHS.We generated...
Abstract Cross-talk between NK cells and dendritic (DCs) is important in Th1 immune responses, including antitumor immunity responses to infections. DCs also play a crucial role polarizing Th2 immunity, but the impact of cell–DC interactions this context remains unknown. In study, we stimulated human monocyte-derived vitro with different pathogen-associated molecules: LPS or polyinosinic–polycytidylic acid, which polarize response, soluble egg Ag from helminth worm Schistosoma mansoni,...
Abstract Membrane contact sites (MCSs) are hubs allowing various cell organelles to coordinate their activities. The dynamic nature of these and small size hinder analysis by current imaging techniques. To overcome limitations, we here designed a series reversible chemogenetic reporters incorporating improved, low-affinity variants splitFAST, studied the dynamics different MCSs at high spatiotemporal resolution, both in vitro vivo . We demonstrated that versatile suit experimental setups...
X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich Syndrome protein (WASp). XLN patients have reduced numbers of cytotoxic cells peripheral blood; however, their capacity to kill tumor remains be determined. Here, we examined NK and T from 2 with harboring activating WASpL270P mutation. patient had increased granzyme B content elevated degranulation IFN-γ production when compared healthy control cells. Murine WASpL272P formed stable...
BackgroundB-cell affinity maturation in germinal center relies on regulated actin dynamics for cell migration and cell-to-cell communication. Activating mutations the cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASp) cause X-linked neutropenia (XLN) with reduced serum level of IgA.ObjectiveWe investigated role B cells XLN pathogenesis.MethodsWe examined from 6 patients, 2 whom had novel R268W S271F WASp. By using immunized mouse models that carry corresponding patient mutations,...
ABSTRACT Signaling via inhibitory KIR/Ly49 receptors preserves natural killer (NK) cell self-tolerance but also conveys NK reactivity towards MHC class-I low target cells in an education process. Here, we demonstrate that mouse by H-2D d regulates transcription of several genes Ly49A+ including Ptpn6 , encoding the phosphatase SHP-1. SHP-1 was highly expressed uneducated cells, which knock-out increased responsiveness. Following NKp46 triggering a higher synaptic abundance phosphorylated...