A5084319746- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Diabetes and associated disorders
- Immunodeficiency and Autoimmune Disorders
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Adrenal Hormones and Disorders
- Neonatal Respiratory Health Research
- Lymphatic System and Diseases
- Childhood Cancer Survivors' Quality of Life
- Glycosylation and Glycoproteins Research
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- Chemokine receptors and signaling
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- Ubiquitin and proteasome pathways
- Congenital gastrointestinal and neural anomalies
- Biomedical Ethics and Regulation
- Myasthenia Gravis and Thymoma
- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
University Children’s Hospital Basel
2016-2025
University of Basel
2016-2025
Board of the Swiss Federal Institutes of Technology
2022-2025
ETH Zurich
2020-2025
University of Oxford
2016-2025
John Radcliffe Hospital
2015-2023
MRC Weatherall Institute of Molecular Medicine
2013-2022
Cancer Research UK Oxford Centre
2020
Cancer Research UK
2020
University Hospital of Basel
2002-2019
The thymic microenvironment is required for T cell development in vivo. However, vitro studies have shown that when hematopoietic progenitors acquire Notch signaling via Delta-like (Dll)1 or Dll4, they differentiate into the lineage absence of a microenvironment. It not clear, however, whether thymus supports specifically by providing signaling. To address this issue, we generated mice with loxP-flanked allele Dll4 and induced gene deletion epithelial cells (TECs). In mutant mice, expression...
Promiscuous gene expression (PGE) by thymic epithelial cells (TEC) is essential for generating a diverse T cell antigen receptor repertoire tolerant to self-antigens, and thus avoiding autoimmunity. Nevertheless, the extent nature of this unusual program within TEC populations single are unknown. Using deep transcriptome sequencing carefully identified mouse subpopulations, we discovered PGE that common between medullary (m) cortical TEC, further elaborated in mTEC, completed mature mTEC...
Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate molecular pathogenesis of organ-specific autoimmunity patients with APS-1, autoantigen responsible for hypoparathyroidism, hallmark APS-1 and its most common endocrinopathy, has not yet been identified.We performed immunoscreening human parathyroid complementary DNA library, using serum...
Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated medulla and contribute to establishment of self-tolerance. However, how medullary accumulation tDCs is regulated involved self-tolerance unclear. We show that chemokine receptor XCR1 expressed by tDCs, whereas thymic epithelial (mTECs) express ligand XCL1. XCL1-deficient mice defective generation naturally occurring regulatory T (nT reg cells). Thymocytes from elicit dacryoadenitis nude mice. mTEC expression XCL1, tDC...
Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This first observed in the thymus, primary lymphoid that generates selects T cells. However, molecular mechanisms underpinning these ageing processes remain unclear. Here, we show mouse leads less efficient selection, decreased self-antigen representation increased receptor repertoire diversity. Using a combination of single-cell RNA-seq lineage-tracing, find...
T cell development is tightly controlled by thymic stromal cells. Alterations in architecture affect maturation and the of self-tolerance. The monogenic autoimmune syndrome APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy) characterized loss self-tolerance to multiple organs. Although mutations regulator (AIRE) gene are responsible for this disease, function AIRE not known. Here we report on spatial temporal pattern murine Aire expression during ontogeny selection....
To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations MMP-2, MMP-3, MMP-8, MMP-9 endogenous inhibitors (TIMP-1 TIMP-2) were measured cerebrospinal fluid (CSF) 27 children with BM. MMP-8 detected 91% 97%, respectively, CSF speci-mens from patients but not control patients. levels higher (P <.05) 5 who developed hearing impairment or secondary epilepsy than those recovered without neurological deficits. Levels correlated TIMP-1...
The lymphokine interleukin-2 (IL-2) is responsible for autocrine cell cycle progression and regulation of immune responses. Uncontrolled secretion IL-2 results in adverse reactions ranging from anergy, to aberrant T activation, autoimmunity. With the use fluorescent situ hybridization single-cell polymerase chain reaction cells with different alleles, expression mature thymocytes was found be tightly controlled by monoallelic expression. Because encoded at a nonimprinted autosomal locus,...
ABSTRACT T-cell development is under the tight control of thymic microenvironments. Conversely, integrity microenvironments depends on physical presence developing thymocytes, a phenomenon designated as ‘thymic crosstalk’. We now show, using three types immunodeficient mice, i.e. CD3ε transgenic RAGnull mice and RAGnull-bone-marrow-transplanted that point in lymphoid where triple negative (CD3−,CD4−,CD8−) thymocytes progress from CD44+CD25− towards CD44− CD25+, influences epithelial cells,...
The thymus provides multiple microenvironments that are essential for the development and repertoire selection of T lymphocytes. thymic cortex induces generation positive lymphocytes, whereas medulla establishes self-tolerance among positively selected Cortical epithelial cells (cTECs) medullary TECs (mTECs) constitute major stromal structurally form functionally characterize medulla, respectively. cTECs mTECs both derived from endodermal epithelium third pharyngeal pouch. However, molecular...