A5005299083- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Reproductive System and Pregnancy
- COVID-19 Clinical Research Studies
- Mesenchymal stem cell research
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Long-Term Effects of COVID-19
- Phagocytosis and Immune Regulation
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Immune cells in cancer
- Animal testing and alternatives
- COVID-19 and Mental Health
- Eosinophilic Esophagitis
- Olfactory and Sensory Function Studies
- Cytomegalovirus and herpesvirus research
- Veterinary Pharmacology and Anesthesia
- Respiratory viral infections research
- Viral Infections and Vectors
- Single-cell and spatial transcriptomics
- Endometriosis Research and Treatment
- Immune responses and vaccinations
- Anesthesia and Neurotoxicity Research
Karolinska Institutet
2015-2025
Karolinska University Hospital
2015-2024
Integrated Cardio Metabolic Centre
2023
Freie Universität Berlin
2016-2018
Medizinische Hochschule Hannover
2009-2014
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as marker differentiates CD8+ Trm on compartmental and functional basis. In human skin epithelia, CD8+CD49a+ produced interferon-γ, whereas CD8+CD49a− interleukin-17 (IL-17). addition, from healthy rapidly induced the expression of effector molecules perforin granzyme B when stimulated with IL-15, thereby promoting strong cytotoxic response....
Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host and interpret disease pathogenesis. Natural killer (NK) cells are effector lymphocytes that respond acute viral infections but might also contribute immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets peripheral blood patients. This pattern was mirrored scRNA-seq signatures bronchoalveolar lavage from Unsupervised high-dimensional analysis...
Abstract Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage hepatic CD49a+DX5− with adaptive-like features. Development this cell is, contrast to conventional cells, dependent on T-bet but not Eomes. In study, we describe identification T-bet+Eomes−CD49a+ subset readily detectable human liver, afferent or efferent venous peripheral blood. Human intrahepatic CD49a+ express killer Ig-like receptor and NKG2C, indicative having undergone...
MAIT cell activation and decline in blood are associated with COVID-19 severity, features that dynamically recover convalescence.
The study of human macrophages and their ontogeny is an important unresolved issue. Here, we use a humanized mouse model expressing cytokines to dissect the development lung from hematopoiesis in vivo. Human CD34+ hematopoietic stem progenitor cells (HSPCs) generated three macrophage populations, occupying separate anatomical niches lung. Intravascular cell labeling, transplantation, fate-mapping studies established that classical CD14+ blood monocytes derived HSPCs migrated into tissue gave...
Dendritic cells (DCs) and monocytes are crucial mediators of innate adaptive immune responses during viral infection, but misdirected by these may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate severe COVID-19. We provide a deep comprehensive map the MNP landscape A redistribution monocyte subsets toward intermediate general decrease circulating DCs was...
The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map healthy human blood- tissue-derived NK cells, with temporal resolution fate-specific expression gene-regulatory networks defining differentiation. Transfer learning facilitated incorporation tumor-infiltrating transcriptomes (39...
Abstract Objective Rituximab is a therapeutic anti‐CD20 antibody used for in vivo depletion of B cells proliferative and autoimmune diseases. However, the mechanisms action are not fully understood, since all therapy‐mediated effects can be explained by antibody‐secreting cells. In addition to cells, there also small population T coexpressing CD20 individuals. This study was conducted examine phenotype function CD3+CD20+ patients with rheumatoid arthritis (RA) healthy controls. Methods The...
The human fetal immune system is naturally exposed to maternal allogeneic cells, antibodies, and pathogens. As such, it faced with a considerable challenge respect the balance between reactivity tolerance. Here, we show that natural killer (NK) cells differentiate early in utero are highly responsive cytokines antibody-mediated stimulation but respond poorly HLA class I–negative target cells. Strikingly, expression of killer-cell immunoglobulin-like receptors (KIRs) did not educate NK...
Abstract Human lung tissue-resident NK cells (trNK cells) are likely to play an important role in host responses towards viral infections, inflammatory conditions and cancer. However, detailed insights into these still largely lacking. Here we show, using RNA sequencing flow cytometry-based analyses, that subsets of human CD69 + CD16 − display hallmarks tissue-residency, including high expression CD49a, CD103, ZNF683 , reduced SELL S1PR5 KLF2/3 . CD49a functionally competent, produce IFN-γ,...
Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there lack consensus regarding what methods killing humane for species stages development. In 2013, international group researchers stakeholders met at Newcastle University, United Kingdom discuss the latest research which could currently be considered most commonly used (mice, rats zebrafish). They...
Human adaptive-like "memory" CD56dimCD16+ natural killer (NK) cells in peripheral blood from cytomegalovirus-seropositive individuals have been extensively investigated recent years and are currently explored as a treatment strategy for hematological cancers. However, of solid tumors remains limited due to insufficient NK cell tumor infiltration, it is unknown whether large expansions that equipped tissue residency homing exist tissues. Here, we show human lung contains CD56brightCD16- with...
Few approaches have been made toward exploring autologous NK cells in settings of cancer immunotherapy. Here, we demonstrate the feasibility infusing multiple doses ex vivo activated and expanded patients with myeloma (MM) post-autologous stem cell transplantation. Infused were detected circulation up to 4 weeks after last infusion. Elevations plasma granzyme B levels observed following each consecutive Moreover, increased bone marrow All measurable had objective, detectable responses...
In the European Union (EU) millions of laboratory mice are used and killed for experimental other scientific purposes each year. Although controversially discussed, use carbon dioxide (CO2) is still permitted killing rodents according to Directive 2010/63/EU. Within scope refinement, our aim was investigate if isoflurane sevoflurane an appropriate alternative method CO2 in mice. Different concentrations (filling rates 20%, 60%, 100%; 20, 60, 100), (Iso 2%, 5%) (Sevo 4.8%, 8%) were compared...
NK cells in the human lung respond to influenza A virus- (IAV-) infected target cells. However, detailed functional capacity of and peripheral blood remains be determined IAV other respiratory viral infections. Here, we investigated effects infection on vitro ex vivo following clinical infection. lung- blood-derived mononuclear induced cell hyperresponsiveness K562 cells, including increased degranulation cytokine production particularly CD56brightCD16- subset Furthermore, CD16- showed...
Despite animal models showing that natural killer (NK) cells are important players in the early defense against many viral infections, NK cell response is poorly understood humans. Here we analyze phenotype, temporal dynamics, regulation and trafficking of a patient cohort with acute dengue virus infection. robustly activated proliferate during first week after symptom debut. Increased IL-18 levels plasma induced skin blisters DENV-infected patients, as well concomitant signaling downstream...
Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, potential detrimental effects on integrity lung tissue. Despite comprising largest fractions circulating lymphocytes in rather little is known about how peripheral blood natural killer (NK) cell T subsets are equipped for lung-homing COVID-19 influenza. Here, we provide detailed comparative analysis NK patients infected or virus, focusing protein gene...
Mucosal-associated invariant T (MAIT) cells are unconventional that recognize microbial riboflavin pathway metabolites presented by evolutionarily conserved MR1 molecules. We explored the human MAIT cell compartment across organ donor–matched blood, barrier, and lymphoid tissues. population size was donor dependent with distinct tissue compartmentalization patterns adaptations: Intestinal CD103 + resident an immunoregulatory CD39 high CD27 low profile, whereas expressing NCAM1/CD56 dominated...
First isolated from bone marrow, mesenchymal stem or stromal cells (MSC) were shown to be present in several postnatal and extraembryonic tissues as well a large variety of fetal (e.g., fatty tissue, dental pulp, placenta, umbilical cord blood, tissue). In this study, an optimized protocol for the expansion MSC-like whole tissue under xeno-free culture conditions is proposed. Different calf sera human serum (HS) compared with regard cell proliferation MSC marker stability long-term...
Abstract NK cells play an important role in the defense against viral infections. However, little is known about regulation of cell responses during first days acute infections humans. In this study, we used live attenuated yellow fever virus (YFV) vaccine 17D as a human vivo model to study temporal dynamics and infection. YFV induced robust response vivo, with early activation peak function at day 6, followed by delayed Ki67 expression, which was indicative proliferation, 10. The correlated...
Lung cancer is a leading cause of cancer-related death worldwide. Despite recent advances in tissue immunology, little known about the spatial distribution tissue-resident lymphocyte subsets lung tumors. Using high-parameter flow cytometry, we identified an accumulation lymphocytes including NK (trNK) cells and CD8+ memory T (TRM) toward center human non-small cell carcinomas (NSCLC). Chemokine receptor expression patterns indicated different modes tumor-infiltration and/or residency between...
Human NK cells can be subdivided into CD56(dim) and CD56(bright) cells, which exhibit different phenotypical functional characteristics. As murine lack CD56 or a distinct correlate, direct comparative studies of in mice humans are limited. Although CD27 is currently proposed as feasible subset marker mice, we assume that the usage this alone insufficient. We rather investigated expression chemokine receptor CXCR3 for its suitability distinguishing NK-cell subsets with simultaneous...