Jakob Theorell

Jakob Theorell
Karolinska University Hospital | Karolinska

MD/PhD student

About

37
Publications
2,980
Reads
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1,558
Citations

Publications

Publications (37)
Article
Full-text available
During early pregnancy, decidual innate lymphoid cells (dILCs) interact with surrounding maternal cells and invading fetal extravillous trophoblasts (EVT). Here, using mass cytometry, we characterise five main dILC subsets: decidual NK cells (dNK)1–3, ILC3s and proliferating NK cells. Following stimulation, dNK2 and dNK3 produce more chemokines tha...
Article
Full-text available
How antibodies naturally acquired during Plasmodium falciparum infection provide clinical immunity to blood-stage malaria is unclear. We studied the function of natural killer (NK) cells in people living in a malaria-endemic region of Mali. Multi-parameter flow cytometry revealed a high proportion of adaptive NK cells, which are defined by the loss...
Article
Full-text available
Technological advances have facilitated an exponential increase in the amount of information that can be derived from single cells, necessitating new computational tools that can make such highly complex data interpretable. Here, we introduce DEPECHE, a rapid, parameter free, sparse k-means-based algorithm for clustering of multi- and megavariate s...
Data
Heatmaps comparing the golden standard partitions to the DEPECHE partitions for A) the 32-variate Levine dataset and B) the 35166-variate Björklund dataset. Red color indicates large overlap, blue color indicates low overlap between a gold standard-vs-DEPECHE cluster pair. Numbers in heatmaps denote percent of the golden standard cluster present in...
Data
Algorithm comparisons. For all graphs, the x-axis shows the algorithms and the y-axis shows the Adjusted Rand Index comparing the clustering result with the golden standard clustering. Below each graph is the average computational time in seconds for the benchmarking performed on a laptop computer with 4 2.8 GHz Intel Core i7 processors. A) Subsamp...
Data
The code used generate all figures. (ZIP)
Data
Information on how to retrieve the data used for this study. (PDF)
Data
A comparison of classical K-means, sparse K-means and DEPECHE. A: Overlap between true clusters and clusters generated with classical k-means, sparse K-means, or DEPECHE. Numbers in heatmaps denote percent of the true cluster present in the generated cluster in question. Red color indicates high overlap, blue color low overlap. B: Total loadings fo...
Preprint
Full-text available
Technological advances have facilitated an exponential increase in the amount of information that can be derived from single cells, necessitating new computational tools that can make this highly complex data interpretable. Here, we introduce DEPECHE, a rapid, parameter free, sparse k-means-based algorithm for clustering of multi-and megavariate si...
Article
Full-text available
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Pr...
Article
Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and natural killer (NK) cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that p...
Article
Full-text available
Natural killer (NK) cells have long been considered short-lived effectors of innate immunity. However, recent animal models and human studies suggest that subsets of NK cells have adaptive features. We investigate clonal relationships of various NK-cell subsets, including the adaptive population, by taking advantage of naturally occurring X-linked...
Article
Full-text available
Introduction Myelodysplastic syndromes (MDS) are a group of clonal bone marrow disorders, with dysplasia, cytopenias and increased risk of progression to acute myeloid leukemia. A dysregulated immune system precipitates MDS, and to gain insights into the relevance of cytotoxic T lymphocyte (CTL) in this process, we examined the frequency and functi...
Chapter
In signaling cascades downstream of NK cell activating receptor engagement, Ca 2+ ions are pivotal second messengers for NK cell cytotoxicity as well as cytokine production. Upon cellular activation, intracellular mobilization of Ca²⁺ ions initially involves depletion of endoplasmic reticulum stores, leading to subsequent Ca²⁺ influx through specif...
Article
Full-text available
Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and...
Article
Natural killer (NK) cells are lymphocytes that participate in different facets of immunity. They can act as innate sentinels through recognition and eradication of infected or transformed target cells, so-called immunosurveillance. In addition, they can contain immune responses through the killing of other activated immune cells, so-called immunore...
Article
Multi-color flow cytometry represents an important tool for characterization of immune cell phenotype and function. In humans, this technique is most often applied to studies of cells obtained from peripheral blood. However, in many human disease conditions, peripheral tissues are the preferred sites for investigation. Such is the case, e.g., in qu...
Article
The mechanisms underlying human natural killer (NK) cell phenotypic and functional heterogeneity are unknown. Here, we describe the emergence of diverse subsets of human NK cells selectively lacking expression of signaling proteins after human cytomegalovirus (HCMV) infection. The absence of B and myeloid cell-related signaling protein expression i...
Article
Objective Recently we serendipitously identified a patient with systemic lupus erythematosus (SLE) who was positive for autoantibodies to CD94/natural killer receptor group 2A (NKG2A). The present study was undertaken to investigate the occurrence and function of autoantibodies targeting lectin-like NK cell receptors in SLE.Methods Sera from 203 SL...
Article
Natural killer (NK) cells mediate defense against neoplastic as well as infected cells. Yet, how their effector functions are affected by the large variety of pharmacological compounds commonly in use has not been investigated systematically. Here, we screened 1,200 in-use or previously approved drugs for their biological effect on freshly isolated...
Article
Full-text available
During childhood, infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) can occur in close temporal proximity. Active, as well as latent, CMV infection is associated with enlarged subsets of differentiated natural killer (NK) and cytotoxic T cells. How EBV infection may influence CMV-driven immune differentiation is not known. We found...
Article
Patients with systemic lupus erythematosus (SLE) display an activated type I IFN system due to unceasing IFN-α release from plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). NK cells strongly promote the IFN-α production by pDCs; therefore, we investigated surface molecules that could be involved in t...
Article
Objectives: To characterize a novel anti-NKG2A autoantibody detected in a patient with SLE during a severe flare, and in a cross-sectional study investigate the occurrence of such autoantibodies in patients with SLE and primary SS (pSS). Methods: Serum or IgG from patients with SLE, pSS and healthy volunteers were assayed for blocking of anti-NK...
Article
Full-text available
Cytotoxic lymphocytes, encompassing cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, kill pathogen-infected, neoplastic, or certain hematopoietic cells through the release of perforin-containing lytic granules. In the present study, we first performed probability-state modeling of differentiation and lytic granule markers on CD8(+) T c...
Article
Background and objectives Patients with SLE have an activated type I interferon (IFN)-system due to an ongoing IFNα production by plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). The IFNα production is promoted by NK cells via MIP-1β, and LFA-1-mediated cell-cell contact. Because genome-wide linkage...
Article
With an array of activating and inhibitory receptors, natural killer (NK) cells can specifically eradicate infected and transformed cells. Target cell killing is achieved through directed release of lytic granules. Recognition of target cells also induces production of chemokines and cytokines that can coordinate immune responses. Upon contact with...
Article
An early step in immunosurveillance by cytotoxic lymphocytes is leukocyte functional antigen (LFA)-1-dependent adhesion to target cells, which is promoted by inside-out signals from receptors such as the T cell receptor and a variety of natural killer (NK) cell activating receptors. Inside-out signals induce a conformational change in LFA-1, result...

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Projects

Projects (2)
Archived project
Project
A clinical project of ME/CFS, some biomarkers will be also studied.