A5006790660- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Advanced Breast Cancer Therapies
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Systemic Lupus Erythematosus Research
- Cancer therapeutics and mechanisms
- Immune Response and Inflammation
- Cancer Research and Treatments
- Synthesis and Biological Evaluation
- CAR-T cell therapy research
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Nanoplatforms for cancer theranostics
- Lymphoma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Pluripotent Stem Cells Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chronic Lymphocytic Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Diabetes and associated disorders
- RNA Interference and Gene Delivery
Karolinska Institutet
2014-2024
Karolinska University Hospital
2016-2024
Rockefeller University
2008-2013
The anti-inflammatory activity of intravenous Ig (IVIG) results from a minor population the pooled IgG molecules that contains terminal α2,6-sialic acid linkages on their Fc-linked glycans. These properties can be recapitulated with fully recombinant preparation appropriately sialylated Fc fragments. We now demonstrate these Fcs require specific C-type lectin, SIGN-R1, (specific ICAM-3 grabbing non-integrin-related 1) expressed macrophages in splenic marginal zone. Splenectomy, loss SIGN-R1...
Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation inflammation, but...
Apoptotic cells are considered to be a major source for autoantigens in autoimmune diseases such as systemic lupus erythematosus (SLE). In agreement with this, defective clearance of apoptotic has been shown increase disease susceptibility. Still, little is known about how cell–derived self-antigens activate autoreactive B and where this takes place. study, we find that taken up by specific scavenger receptors expressed on macrophages the splenic marginal zone mice deficient these have lower...
Faulty activation of autoreactive B cells is a hallmark autoimmune diseases like systemic lupus erythematosus (SLE). An important feature restricting efficient removal apoptotic material. Mounting evidence also connects primary defect in invariant natural killer T (iNKT) to disease development. However, exactly how this unconventional cell subset involved remains be defined. Here, we identify suppressive role for iNKT model where autoantibody production triggered by an increased load...
FNDC4 is a secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 robustly upregulated in several mouse models of inflammation as well human inflammatory conditions. Specifically, levels are increased locally at inflamed sites intestine bowel disease patients. Interestingly, administration recombinant model induced colitis markedly reduces severity compared mice injected control protein. Conversely, lacking develop more severe...
Background: Atherosclerosis progression is modulated by interactions with the adaptive immune system. Humoral immunity can help protect against atherosclerosis formation; however, existence, origin, and function of putative atherogenic antibodies are controversial. How such atherosclerosis-promoting could affect specific composition stability plaques, as well vasculature generally, remains unknown. Methods: We addressed overall contribution to plaque formation, composition, in vivo (1) mice...
Rheumatoid arthritis (RA) associated anti-citrullinated protein autoantibodies (ACPA) target a wide range of modified proteins. Citrullination occurs during physiological processes such as apoptosis, yet little is known about the interaction ACPA with nuclear antigens or apoptotic cells. Since uncleared cells and neutrophil extracellular trap (NET) products have been postulated to be central sources autoantigen immunostimulation in autoimmune disease, we sought characterize anti-nuclear...
Recognition of microbial components by TLR, key sensors infection, leads to induction inflammatory responses. We found that, in vivo, TLR4 engagement LPS induces up-regulation the class A scavenger receptors (SR) macrophage receptor with a collagenous structure (MARCO) and SR-A, which occurs, at least case MARCO, via both MyD88-dependent -independent pathways. When challenging mice low dose followed high dose, SR-deficient showed higher survival rate than WT mice. This was paired increased...
Neutrophils are the most abundant immune cells found in actively inflamed joints of patients with rheumatoid arthritis (RA), and animal models for RA depend on neutrophils induction joint inflammation. Exogenous IL-4 IL-13 protect mice from antibody-mediated inflammation, although mechanism is not understood. display a very strong basal expression STAT6, which responsible signaling following exposure to IL-13. Still, role neutrophil biology has been well studied. This can be explained by low...
Inactivating p53 mutations are the most abundant genetic alterations found in cancer. Here we show that CRISPR/Cas9-induced double-stranded DNA breaks enrich for cells deficient and genes of a core CRISPR-p53 tumor suppressor interactome. Such enrichment could predispose to cancer development thus pose challenge clinical CRISPR use. Transient inhibition suppress with these mutations. The level damage response induced by an sgRNA influenced p53-deficient be relevant parameter design limit...
Defined particles carrying tightly bound allergens at high density have been suggested as alternatives in allergy vaccination. Carbohydrate based (CBP), sized 2 microm, provide a platform for covalent coupling of allergens.To investigate the mechanisms antigen presentation by CBP, well cellular and humoral responses after vaccination with major cat allergen Fel d 1, covalently coupled to CBP.Mice (n = 10/group) were subcutaneously vaccinated CBP-rFel CBP or phosphate buffer saline (PBS)...
Objective Rituximab-mediated late-onset neutropenia (LON) has been described in various diseases. We investigated its occurrence, consequences and contributing factors patients with systemic lupus erythematosus (SLE). Methods Rituximab-treated from the Karolinska University Hospital ( n = 107) were surveyed. LON was defined as an absolute neutrophil count <1500 cells/μl, occurring four weeks to two years following rituximab treatment, or later during sustained B-cell depletion. Serum...
Staphylococcus aureus is a leading cause of skin and soft issue infection, but paradoxically, it also transiently, often harmlessly, colonizes human skin. An obstacle to understanding this contradiction has been shortage in vivo models reproducing the unique structure immunology In work, we developed humanized model study how healthy adult responds colonizing methicillin-resistant S. (MRSA). We demonstrate importance outer stratum corneum as major site bacterial colonization noninvasive MRSA...
Abstract We aimed to search for common features in the autoreactive T cell receptor (TCR) repertoire patients with rheumatoid arthritis (RA), focusing on newly identified candidate antigen citrullinated Tenascin C (cit-TNC). Mononuclear cells from peripheral blood or synovial fluid of eight RA-patients positive RA-associated HLA-DRB1*04:01 allele were in-vitro cultured recently peptides C. Antigen-specific isolated using peptide-HLA tetramer staining and subsequently single-cell sequenced...
Background/Aims: Inflammation is a major and critical component of the lung pathology in hereditary disease cystic fibrosis. The molecular mechanisms chronic inflammation fibrosis require definition. Methods: We used several genetic mouse models to test role iNKT cells ceramide pulmonary mice. was determined by cytokine profil abundance inflammatory lung. Results: Here we provide new concept how individuals with initiated. show that mice mutation Cftr gene provokes significant up-regulation...
The anti-inflammatory drug high-dose intravenous immunoglobulin, widely used to suppress inflammation, depends on a specific α-2,6-sialylated glycoform of IgG Fc induce Interleukin 4 (IL-4) and Signal Transducer Activator Transcription 6 (STAT6) signaling for its activity. Here we show that activities IL-4 can be attributed the direct action this cytokine myeloid effector cells, depending their expression receptor alpha chain (IL-4Rα/CD124). However, in basal state, these cells express low...
To kill target cells, natural killer (NK) cells organize signaling from activating and inhibitory receptors to form a lytic synapse. Wiskott-Aldrich syndrome (WAS) patients have loss-of-function mutations in the actin regulator WASp suffer immunodeficiency with increased risk develop lymphoreticular malignancies. NK WAS fail synapses, however, functional outcome vivo remains unknown. Here, we show that KO had decreased capacity degranulate produce IFNγ upon NKp46 stimulation this was...
Proteins subjected to post-translational modifications, such as citrullination, carbamylation, acetylation or malondialdehyde (MDA)-modification are targeted by autoantibodies in seropositive rheumatoid arthritis (RA). Epidemiological and experimental studies have both suggested the pathogenicity of humoral autoimmunity, however, molecular mechanisms triggered anti-modified protein antibodies remained be identified. Here we describe detail pathways induced anti-MDA modified that were...
Abstract Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating MS challenging due to limited insights into the underlying mechanisms. We examined molecular changes associated primary (PPMS) using cross-tissue (blood post-mortem brain) multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of 1q21.1 locus, controlled by...