A5062546114- Mast cells and histamine
- Immune Cell Function and Interaction
- interferon and immune responses
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Asthma and respiratory diseases
- IL-33, ST2, and ILC Pathways
- Food Allergy and Anaphylaxis Research
- Viral Infections and Vectors
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Response and Inflammation
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- Allergic Rhinitis and Sensitization
- Inflammasome and immune disorders
- Cytomegalovirus and herpesvirus research
- Cytokine Signaling Pathways and Interactions
- Dermatology and Skin Diseases
- Microscopic Colitis
- Wound Healing and Treatments
- Systemic Lupus Erythematosus Research
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
University Hospital Heidelberg
2022-2025
Heidelberg University
2022-2025
German Center for Infection Research
2024
Miltenyi Biotec (Germany)
2024
University Hospital Carl Gustav Carus
2014-2023
TU Dresden
2014-2023
Institute of Immunology
2016-2022
Carl Gustav Carus-Institut
2010-2018
Faculty of 1000 (United States)
2018
University of Cologne
2003-2016
Influx of macrophages plays a crucial role in tissue repair. However, the precise function during healing response has remained subject debate due to their functional dichotomy as effectors both injury and We tested hypothesis that recruited diverse phases skin repair after mechanical exert specific functions restore integrity. For this purpose, we developed mouse model allows conditional depletion sequential stages response. Depletion restricted early stage (inflammatory phase)...
Clonal composition and T cell receptor (TCR) repertoire of CD4+ CD8+ cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were determined with unprecedented resolution at the level single cells. Individual or isolated from frozen sections lesional tissue by micromanipulation subjected to target amplification TCR-β gene rearrangements. This strategy allows assignment a TCR variable region (V region) sequence particular which it was amplified. Sequence analysis revealed...
Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a C5a, endothelin 1, induced human rapidly to secrete small relatively spherical structures, a pattern consistent with secretion individual...
Interleukin (IL)-10 is elevated in cancer and thought to contribute immune tolerance tumor growth. Defying these expectations, the adoptive transfer of IL-10-expressing T cells mice with polyposis attenuates microbial-induced inflammation suppresses polyposis. To gain better insights into how IL-10 impacts polyposis, we genetically ablated APC(Δ468) compared effects treatment broad-spectrum antibiotics. We found that regulatory (Treg) were a major cellular source both healthy polyp-bearing...
IL-10 plays a central role in restraining the vigor of inflammatory responses, but critical cellular sources this counter-regulatory cytokine remain speculative many disease models. Using novel transcriptional reporter mouse, we found an unexpected predominance B cells (including plasma cells) among IL-10-expressing peripheral lymphoid tissues at baseline and during diverse models vivo immunological challenge. Use cell-specific knockout mouse revealed that cell-derived nonredundantly...
Cytosolic detection of DNA is crucial for the initiation antiviral immunity but can also cause autoimmunity in context endogenous nucleic acids being sensed. Mutations human 3' repair exonuclease 1 (TREX1) have been linked to type I IFN-associated autoimmune disease Aicardi-Goutières syndrome. The exact mechanisms driving unabated IFN responses absence TREX1 are only partly understood, it appears likely that accumulation species triggers a cell-autonomous immune response by activating...
Ribonucleases H (RNases H) are endonucleases which cleave the RNA moiety of RNA/DNA hybrids. Their function in mammalian cells is incompletely understood. RNase H2 mutations cause Aicardi-Goutières syndrome, an inflammatory condition clinically overlapping with lupus erythematosus. We show that essential mouse embryonic development. H2–deficient proliferated slower than control and accumulated G2/M phase due to chronic activation a DNA damage response associated increased frequency...
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in genes encoding genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder shares features with autoimmune disease systemic lupus erythematosus (SLE). Here we determined heterozygous parents of AGS patients exhibit an intermediate phenotype and demonstrated genetic association between rare RNASEH2 sequence...
Wound healing is a coordinated process that initially relies on pro-inflammatory macrophages, followed by pro-resolution function of these cells. Changes in cellular metabolism likely dictate distinct activities, but the nature changes has been unclear. Here, we profiled early- versus late-stage skin wound macrophages mice at both transcriptional and functional levels. We found glycolytic early phase not sufficient to ensure productive repair. Instead, combining conditional disruption...
Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, found that in aged mice, neutrophils adhered to vascular endothelium inflamed tissues but exhibited a high frequency reverse transendothelial migration (rTEM). This retrograde breaching by was governed enhanced production chemokine CXCL1 from mast cells localized at endothelial cell (EC) junctions. Increased EC expression atypical...
Macrophages populate every organ during homeostasis and disease, displaying features of tissue imprinting heterogeneous activation. The disconnected picture macrophage biology that has emerged from these observations is a barrier for integration across models or with in vitro activation paradigms. We set out to contextualize heterogeneity mouse tissues inflammatory conditions, specifically aiming define common framework built predictive model which we mapped the macrophages 12 25 biological...
RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition its positive regulatory role, also restricts recognition through unknown mechanisms, as patients deficient suffer from neuroinflammation. Consistent with this, mice lacking exhibit interferon-dependent neuroinflammation, impaired hematopoiesis, and splenomegaly....
We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to clarify their unusual clinical presentation but were subsequently confirmed have typical sclerosis. One biopsy specimens been previously investigated by microdissection single-cell PCR determine clonal composition brain-infiltrating cells at level. Using complementarity-determining region 3...
Interleukin (IL)-10 is a regulator of inflammatory responses and secreted by variety different cell types including T cells. regulatory cells have been shown to suppress immune IL-10–dependent, but also IL-10–independent, mechanisms. Herein, we address the role cell–derived IL-10 in mice with an inactivation gene restricted generated Cre/loxP-mediated targeting gene. Splenocytes from this cell–specific mutant secrete increased amounts proinflammatory cytokines after activation vitro compared...
Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously represents a cell lymphoma. In subset cHD, however, H/RS expressing T cell–associated proteins may be candidates for alternative lineage derivation. Single with cytotoxic phenotype were micromanipulated from three cases analyzed by single polymerase chain reaction immunoglobulin heavy (IgH) light...
Infection with the malaria parasite, Plasmodium, is characterized by excessive inflammation. The establishment of a precise balance between pro- and anti-inflammatory responses critical to guarantee control parasite survival host. IL-10, key regulatory cytokine produced many cells immune system, has been shown protect mice against pathology during acute Plasmodium0 chabaudi AS model malaria. However, cellular source IL-10 still unknown. In this article, we demonstrate that T cell-derived...
Mast cells are important effectors of type I allergy but also essential regulators innate and adaptive immune responses. The aim this study was to develop a Cre recombinase-expressing mouse line that allows mast cell-specific inactivation genes in vivo. Following BAC transgenic approach, expressed under the control cell protease (Mcpt) 5 promoter. Mcpt5-Cre mice were crossed ROSA26-EYFP excision reporter strain. Efficient Cre-mediated recombination observed from peritoneal cavity skin while...