A5024922998- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- Adrenal Hormones and Disorders
- Immune Response and Inflammation
- Viral-associated cancers and disorders
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
- Immune responses and vaccinations
- Asthma and respiratory diseases
- Gut microbiota and health
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced biosensing and bioanalysis techniques
- Dermatology and Skin Diseases
- Diabetes and associated disorders
- Cancer Research and Treatments
- Erythrocyte Function and Pathophysiology
- RNA Research and Splicing
- Hematopoietic Stem Cell Transplantation
- Zebrafish Biomedical Research Applications
- Viral Infections and Immunology Research
Czech Academy of Sciences, Institute of Molecular Genetics
2015-2025
Weizmann Institute of Science
2018-2024
Rockefeller University
2023
Institute of Molecular Genetics
2018-2022
The autoimmune regulator (Aire) serves an essential function for T cell tolerance by promoting the "promiscuous" expression of tissue antigens in thymic epithelial cells. Aire is also detected rare cells peripheral lymphoid organs, but identity these poorly understood. Here, we report that protein-expressing lymph nodes exhibit typical group 3 innate (ILC3) characteristics such as morphology, absence "classical" hematopoietic lineage markers, and dependence on RORγt. Aire+ are more frequent...
Abstract The development of thymic regulatory T cells (Treg) is mediated by Aire-regulated self-antigen presentation on medullary epithelial (mTECs) and dendritic (DCs), but the cooperation between these still poorly understood. Here we show that signaling through Toll-like receptors (TLR) expressed mTECs regulates production specific chemokines other genes associated with post-Aire mTEC development. Using single-cell RNA-sequencing, identify a new CD14 + Sirpα population monocyte-derived...
The mechanisms of central tolerance, which rely on the presentation self-antigens by medullary thymic epithelial cells (mTECs) and DCs, prevent autoimmunity eliminating self-reactive T-cells. While mTECs produce in an autonomous manner, DCs acquire them from via cooperative antigen transfer (CAT). Our recent data showed that preferential pairing occurs between distinct subsets CAT, providing a rationale for existence molecular determinants control such outcome tolerance. Here, we compared...
Human herpesvirus-6 (HHV-6) A and B are ubiquitous betaherpesviruses, infecting the majority of human population. They encompass large genomes our understanding their protein coding potential is far from complete. Here, we employ ribosome-profiling systematic transcript-analysis to experimentally define HHV-6 translation products. We identify hundreds new open reading frames (ORFs), including upstream ORFs (uORFs) internal (iORFs), generating a complete unbiased atlas proteome. By...
Interleukin (IL)-17 protects epithelial barriers by inducing the secretion of antimicrobial peptides. However, effect IL-17 on Paneth cells (PCs), major producers peptides in small intestine, is unclear. Here, we show that targeted ablation receptor (IL-17R) PCs disrupts their functions and decreases frequency ileal PCs. These changes become more pronounced after colonization with segmented filamentous bacteria. Mice lack IL-17R an increased inflammatory transcriptional profile ileum along...
Medullary thymic epithelial cells (mTECs), which produce and present self-antigens, are essential for the establishment of central tolerance. Since mTEC numbers limited, their function is complemented by dendritic (DCs), transfer mTEC-produced self-antigens via cooperative antigen (CAT). While CAT required effective T cell selection, many aspects remain enigmatic. Given recently described heterogeneity mTECs DCs, it unclear whether acquisition from a particular TEC subset mediated...
The initiation of T-cell signaling is critically dependent on the function member Src family tyrosine kinases (SFKs), Lck. Upon TCR triggering, Lck kinase activity induces nucleation signal-transducing hubs that regulate formation complex network and cytoskeletal rearrangement. In addition, delivery requires rapid targeted membrane redistribution, but mechanism underpinning this process largely unknown. To gain insight into process, we considered previously described proteins could assist in...
Rho-associated coiled-coil kinase (ROCK) protein is a central that regulates numerous cellular functions, including polarity, motility, proliferation, and apoptosis. Here, we demonstrate ROCK has antiviral properties, inhibition of its activity results in enhanced propagation human cytomegalovirus (HCMV). We show during HCMV infection, ROCK1 translocates to the nucleus concentrates nucleolus, where it colocalizes with stress-related chaperone heat shock cognate 71-kDa (Hsc70). Gene...
Abstract Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence spatially and temporally overlap phenotypic markers are often shared, the specifics regarding origin, development, lineage restriction mutual relationships have not been fully determined. The identification wave-specific would aid to resolve these uncertainties. Here, we show that toll-like receptors (TLRs) expressed during early mouse embryogenesis. We...
Abstract Genetic screens have transformed our ability to interrogate cellular factor requirements in infection, yet current approaches are limited their sensitivity, biased towards early stages of infection and provide only simplistic phenotypic information which is often based on infected cell survival. Here, by engineering human cytomegalovirus express sgRNA libraries directly from the viral genome, we developed a sensitive, versatile, centric approach that allows profiling different along...
Abstract Medullary thymic epithelial cells (mTECs) which produce and present self-antigens are essential for the establishment of central tolerance. Since mTEC numbers limited, their function is complemented by dendritic (DCs), transfer mTEC-produced via cooperative antigen (CAT). While CAT required effective T cell selection, many aspects remain enigmatic. Given recently described heterogeneity mTECs DCs, it unclear whether acquisition from a particular TEC subset mediated preferential...
Hematopoiesis in mammalian embryos proceeds through three successive waves of hematopoietic progenitors. Since their emergence is spatially and temporally overlapping phenotypic markers are often shared, the specifics regarding origin, development, lineage restriction mutual relationships have not been fully determined. The identification wave-specific would aid to resolve these uncertainties. Here, we show that Toll-like receptors (TLRs) expressed during early embryogenesis. We provide...