A5019237927- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CAR-T cell therapy research
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Erythrocyte Function and Pathophysiology
- Cell Adhesion Molecules Research
- Neutropenia and Cancer Infections
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Microtubule and mitosis dynamics
- Acute Myeloid Leukemia Research
- Inflammasome and immune disorders
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- Lymphoma Diagnosis and Treatment
- Spaceflight effects on biology
- Antimicrobial Peptides and Activities
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Streptococcal Infections and Treatments
- Single-cell and spatial transcriptomics
- Cell death mechanisms and regulation
- Lipid Membrane Structure and Behavior
Karolinska Institutet
2018-2023
Swedish Orphan Biovitrum (United States)
2021
University College London
2012-2016
Institut de Pharmacologie et de Biologie Structurale
2011
Centre National de la Recherche Scientifique
2011
High levels of ecto-5′-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, also observed cancer patients who progress on anti–PD-1 immunotherapy. Although regulatory T cells can express CD73 inhibit cell responses via the production adenosine, less is known about expression other populations. We found that tumor-infiltrating NK upregulate frequency these CD73-positive correlated with larger size breast patients. In addition, multiple alternative checkpoint...
The importance of actin dynamics in the activation inflammasome is becoming increasingly apparent. IL-1β, which activated by inflammasome, known to be central pathogenesis many monogenic autoinflammatory diseases. However, evidence from an murine model indicates that IL-18, other cytokine triggered activity, important its own right. In this model, autoinflammation was caused mutation regulatory gene WDR1 We report a homozygous missense two siblings causing periodic fevers with...
Congenital neutropenia is characterized by low absolute neutrophil numbers in blood, leading to recurrent bacterial infections, and patients often require life-long granulocyte CSF (G-CSF) support. X-linked (XLN) caused gain-of-function mutations the actin regulator Wiskott-Aldrich syndrome protein (WASp). To understand pathophysiology XLN role of WASp neutrophils, we here examined 2 mouse models. had reduced myelopoiesis extremely blood number. However, their neutrophils a hyperactive...
Lysosome mobilization is a key cellular process in phagocytes for bactericidal activities and trans-matrix migration. The molecular mechanisms that regulate lysosome are still poorly known. Lysosomes hard to track as they move toward phagosomes throughout the cell volume. In order anticipate regions where lysosomes recruited to, human RAW264.7 macrophages were seeded on surfaces micro-patterned with immune complexes (ICs) 4 μm-side squares. Distances between IC patterns adapted optimize...
Leukocyte adhesion deficiency type I (LAD-I) is a primary immunodeficiency caused by mutations in the ITGB2 gene and characterized recurrent life-threatening bacterial infections. These lead to defective or absent expression of β2 integrins on leukocyte surface, compromising extravasation at sites infection. Three different lentiviral vectors (LVs) conferring ubiquitous preferential CD18 myeloid cells were constructed tested human mouse LAD-I cells. All three hCD18-LVs restored CD11a...
Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together they regulate transcription actin cytoskeleton genes. MKL1 associated with hematologic malignancies immunodeficiency, but its role in B cells unexplored. Here we examined from monozygotic triplets an intronic deletion MKL1, two whom had been previously treated for Hodgkin lymphoma (HL). To investigate B-cell responses the pathogenesis HL, generated Epstein-Barr virus-transformed lymphoblastoid cell...
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...
The next steps of deep space exploration are manned missions to Moon and Mars. For safe for crew members, it is important understand the impact flight on immune system. We studied effects 21 days dry immersion (DI) exposure transcriptomes T cells isolated from blood samples eight healthy volunteers. Samples were collected 7 before DI, at day 7, 14, during after DI. RNA sequencing CD3+ revealed transcriptional alterations across all time points, with most changes occurring 14 DI exposure. At...
Abstract Dendritic cells (DCs) devoid of the actin regulator Wiskott-Aldrich syndrome protein (WASp) show reduced directed migration and decreased formation podosome adhesion structures. We examined DCs expressing a gain-of-function mutation in WASp, WASp L272P, identified X-linked neutropenia patients. Analysis L272P was compared to WASp-deficient examine how activity influences DC migratory responses. In confined space, had increased speed whereas similar average but fluctuations,...
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,...
The actin cytoskeleton is crucial at many junctures of normal immune function, and consequently there are specific regulators dynamics. A growing number primary immunodeficiencies being defined as caused by mutations in the genes encoding these regulators. In addition to immunodeficiency, dysregulation autoinflammation increasingly recognised arise from defects within this pathway.
Lymphomas are the third most common type of malignancy among children, affecting 10%–15% all new childhood cancer patients. divided into three main categories: B (40%) and T (20%) cell lymphomas Hodgkin (HL, 40%). Current treatments based on radiotherapy, chemotherapy, or monoclonal antibodies. Despite effectiveness, these intensive associated with severe adverse effects, including infertility, secondary malignancies, heart failure. Moreover, drug resistance is relapse leads to poor...