A5010988421- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- Single-cell and spatial transcriptomics
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Cancer Genomics and Diagnostics
- Viral Infections and Vectors
- Cytomegalovirus and herpesvirus research
- SARS-CoV-2 and COVID-19 Research
- Long-Term Effects of COVID-19
- Vector-borne infectious diseases
- vaccines and immunoinformatics approaches
- Influenza Virus Research Studies
- Eosinophilic Esophagitis
- Immune responses and vaccinations
- Evolution and Genetic Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Gene Regulatory Network Analysis
- Immune Response and Inflammation
- Diabetes and associated disorders
- Immune cells in cancer
Karolinska Institutet
2016-2025
Karolinska University Hospital
2015-2024
Integrated Cardio Metabolic Centre
2023
University of California, San Francisco
2004-2008
Blood Systems Research Institute
2008
Cancer Research Institute
2007
San Francisco General Hospital
2007
Gladstone Institutes
2004-2006
National Center for Tumor Diseases
2000-2005
Institute of Virology of the Slovak Academy of Sciences
2004
As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, induction such tolerance is thought be attributable deletion self-reactive cells. Here, we show that human fetal takes advantage an additional mechanism: generation regulatory (Tregs) suppress responses. We find substantial numbers maternal cross placenta reside in lymph nodes, inducing development CD4+CD25highFoxP3+ Tregs antimaternal immunity...
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....
Natural killer (NK) cells are known to mount a rapid response several virus infections. In experimental models of acute viral infection, this has been characterized by prompt NK cell activation and expansion followed contraction. contrast model systems, much less is about responses infections in humans. We demonstrate that can rapidly expand persist at highly elevated levels for >60 d after human hantavirus infection. A large part the expanding expressed activating receptor NKG2C were...
ABSTRACT Regulatory T (T R ) cells maintain tolerance to self-antigens and control immune responses alloantigens after organ transplantation. Here, we show that CD4 + CD25 human suppress virus-specific T-cell responses. Depletion of from peripheral blood mononuclear enhances cytomegalovirus immunodeficiency virus antigens. We propose chronic viral infections lead induction suppressive inhibit the antiviral 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...
Although the mammalian immune system is generally thought to develop in a linear fashion, findings avian and murine species argue instead for developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise lymphocyte lineages at different stages development. Here we provide evidence an analogous layered humans. Our results suggest fetal adult T are populations arise from HSCs present We also cell lineage biased toward tolerance. These...
CD8+ T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing differentiation, T-bet and Eomesodermin (Eomes), have previously been shown in mice to differentially regulate part through direct modulation PD-1. Here, we examined the relationship between these expression several inhibitory receptors (PD-1, CD160, 2B4), functional characteristics memory differentiation cells treated The PD-1, 2B4 on total was elevated chronically infected...
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...
Abstract The lung contains numerous specialized cell types with distinct roles in tissue function and integrity. To clarify the origins mechanisms generating heterogeneity, we created a comprehensive topographic atlas of early human development. Here report 83 states several spatially resolved developmental trajectories predict interactions within defined niches. We integrated single-cell RNA sequencing transcriptomics into web-based, open platform for interactive exploration. show gene...
The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed transcriptomics variable, diversity, joining (VDJ) sequences (Spatial VDJ), a method that maps B cell T receptor in human tissue sections. Spatial VDJ captures match canonical distributions amplifies clonal confirmed by orthogonal methods. found congruency between paired chains, computational framework predict pairs, linked the expansion distinct...
Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells the same type has been ascribed stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression impart diversity within type. Studying clonal human lymphocytes mouse brain cells, uncovered a vast different clones vivo. We combined chromatin accessibility...
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...
Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical major complex (MHC) class I molecule which presents restricted set of nonameric peptides, derived mainly from the signal sequence other MHC molecules. It interacts with CD94/NKG2 receptors expressed on surface natural killer (NK) cells and T cell subsets. Here we demonstrate that HLA-E also peptide leader human heat shock protein 60 (hsp60). This gains access to intracellularly, resulting in up-regulated HLA-E/hsp60...
Although human T cells enter the peripheral lymphoid tissues early during fetal development, adaptive immune system in fetus has largely been regarded as functionally immature and unresponsive to stimulation. In this study, we show that depletion of CD4+CD25(high) regulatory (T(Reg)) cells, which are present at high frequency tissues, results vigorous cell proliferation cytokine production vitro, even absence exogenous Analysis CD4+ CD8(+) populations revealed a large subset expressed...