A5031391280- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Gut microbiota and health
- T-cell and B-cell Immunology
- Immune cells in cancer
- Dermatology and Skin Diseases
- Microscopic Colitis
- Digestive system and related health
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Inflammatory Bowel Disease
- Advanced Glycation End Products research
- Advanced Proteomics Techniques and Applications
- Psoriasis: Treatment and Pathogenesis
- Liver Disease Diagnosis and Treatment
- Eosinophilic Esophagitis
- Hedgehog Signaling Pathway Studies
- Liver Diseases and Immunity
- Whipple's Disease and Interleukins
- Mass Spectrometry Techniques and Applications
- Adenosine and Purinergic Signaling
- Gastrointestinal disorders and treatments
- Tumors and Oncological Cases
- Clostridium difficile and Clostridium perfringens research
University Medical Center Hamburg-Eppendorf
2016-2024
Universität Hamburg
2016-2024
Klinik und Poliklinik für Neurologie
2021
University of Göttingen
2012
Universitätsmedizin Göttingen
2012
Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second most deadly cancer by 2040, owing high incidence of metastatic disease and limited responses treatment1,2. Less than half all patients respond primary treatment for PDAC, chemotherapy3,4, genetic alterations alone cannot explain this5. Diet an environmental factor that can influence response therapies, but its role in PDAC unclear. Here, using shotgun metagenomic sequencing metabolomic screening, we show microbiota-derived...
Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving remain unclear. Here we report that CD4+ T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), endogenous inhibitor tissue-protective cytokine IL-22. Using mouse models, demonstrate development requires cell-derived IL-22BP. Lastly, intestinal responsive...
IL-10 is essential to maintain intestinal homeostasis. CD4+ T regulatory type 1 (TR1) cells produce large amounts of this cytokine and are therefore currently being examined in clinical trials as cell therapy patients with inflammatory bowel disease. However, factors molecular signals sustaining TR1 activity still need be identified optimize the efficiency ensure safety these trials. We investigated role signaling mature vivo. Double IL-10eGFP Foxp3mRFP reporter mice transgenic impairment...
During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice treated an antibody were protected from colon-cancer-derived liver lung metastasis formation, while overexpression promoted Mechanistically, acted...
Abstract Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences this short-term consumption are unclear. Here, we show that reiterative switching ‘feast diets’, mimicking our social eating behavior, breaches potential buffering effect intestinal microbiota reorganizes immunological architecture mucosa-associated lymphoid tissues. The first dietary switch was...
Objective There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), chronic disease of the liver characterised by biliary inflammation that leads to strictures fibrosis. Approximately 60%�80% people with PSC will also develop (PSC-IBD). One hypothesis explaining this would be drives IBD. Therefore, our aim was test decipher underlying mechanism. Design Colitis severity analysed in experimental mouse models colitis cholangitis, PSC-IBD. Foxp3 + Treg-cell...
TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue is a beneficial host response to infection, but it can also contribute autoimmunity. The crosstalk between tissue the immune system during an inflammatory key for preserving integrity restoring physiological processes. However, how inflamed regulates magnitude by controlling pro-inflammatory T not well characterized so far. Here we show that accumulating small intestine upon express IL-33...
Abstract Uncontrolled regeneration leads to neoplastic transformation 1–3 . The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal prevent transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datasets two damage models 4,5 using pharmacological, transcriptomics genetic tools, we identified liver X receptor (LXR) pathway activation as a adaptation...
Background & AimsUnregulated activity of interleukin (IL) 22 promotes intestinal tumorigenesis in mice. IL22 binds the antagonist subunit alpha 2 (IL22RA2, also called IL22BP). We studied whether alterations IL22BP contribute to colorectal carcinogenesis humans and mice.MethodsWe obtained tumor nontumor tissues from patients with cancer (CRC) measured levels cytokines by quantitative polymerase chain reaction, flow cytometry, immunohistochemistry. Il22bp messenger RNA colon wild-type,...
Pro-inflammatory CD4 + T cells are major drivers of autoimmune diseases, yet therapies modulating cell phenotypes to promote an anti-inflammatory state lacking. Here, we identify helper 17 (T H 17) plasticity in the kidneys patients with antineutrophil cytoplasmic antibody–associated glomerulonephritis on basis single-cell (sc) receptor analysis and scRNA velocity. To uncover molecules driving polarization plasticity, established vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen...
The characterization of the influence microbiota on development and drug responses during rheumatic diseases has intensified in recent years. role specific bacteria disease become a central research question. Notably, several lines evidence point to distinct microbes, e.g., Prevotella copri (P. copri) being targeted by antibodies clinical phases diseases.In present study, we compiled broad collection human serum samples from individuals at risk developing RA, chronic RA patients as well with...
IL-22 is a potent pro-inflammatory cytokine upregulated in psoriasis and other inflammatory diseases. The function of regulated by the soluble scavenging receptor, binding protein (IL-22BP or IL-22RA2). However, role regulation IL-22BP itself pathogenesis disease remain unclear. We used TLR7 agonist Imiquimod (IMQ) to induce psoriasis-like skin mice found strong downregulation affected as well lymph nodes animals treated with IMQ. also analysed psoriatic patients compared this healthy...
<h3>Background & Aims</h3> The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and pathological consequences infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie severe focal liver damage induced protozoan parasite, <i>Entamoeba histolytica</i>. Here, we analyze contribution to induction subsequent recovery from parasite-induced damage. <h3>Methods</h3> <i>IL-23p19<sup>−/−</sup></i>,...
Abstract Background Primary sclerosing cholangitis (PSC) is a progressive liver disease associated with inflammatory bowel (IBD). The percentage of PSC patients diagnosed concomitant IBD varies considerably between studies. This raises the question whether all would show intestinal inflammation if screened thoroughly, even in absence symptoms. Methods To address this question, we collected biopsies healthy controls (n = 34), 25), PSC-IBD 41), and 51) cross-sectional study carried out...
It was recently shown that ultrashort pulse infrared (IR) lasers, operating at the wavelength of OH vibration stretching band water, are highly efficient for sampling and homogenizing biological tissue. In this study we utilized a tunable nanosecond laser (NIRL) tissue homogenization with subsequent liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis spectrometric proteomics. For first time, performed murine spleen colon An ablation volume 1.1 × 0.4 mm³ (approximately 0.5 µL)...
Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is need for new potential treatment options like immunotherapies. However, the microenvironment in EACs its impact on patient outcome remain be fully understood.mRNA expression levels of pro- anti-inflammatory markers 39 EAC patients without neoadjuvant radio-chemotherapy were measured. Data confirmed using...
Abstract Background High-mobility group box protein 1 [HMGB1] is a ubiquitous nucleoprotein with immune-regulatory properties following cellular secretion or release in sterile and infectious inflammation. Stool serum HMGB1 levels correlate colitis severity colorectal cancer [CRC] progression, yet recent reports indicate that mainly operates as an intracellular determinant of enterocyte fate during colitis, investigations into the roles CRC are lacking. Methods Using mice conditional...
Introduction Reflux promotes esophageal adenocarcinomas (EAC) creating a chronic inflammatory environment. EAC show an increasing incidence in the Western World and median survival rates are still low. The main reasons for poor prognosis despite new multimodal therapies diagnosis of EACs at already advanced stage distant metastases. Hence, we wanted to investigate presence systemic interleukins (IL) their impact on patient prognosis. Material methods Systemic expression levels pro-...
For investigating the molecular physiology and pathophysiology in organs, most exact data should be obtained; if not, organ-specific cell lines are analyzed, or whole organ is homogenized, followed by analysis of its biomolecules. However, morphological organization can addressed, then, best case, composition molecules single cells target analyzed. Laser capture microdissection (LCM) a technique which enables selection specific tissue for further their molecules. LCM time-consuming...
T regulatory type 1 (Tr1) cells, which are defined by their function, lack of Foxp3, and high expression IL-10, CD49b, LAG-3, known to be able suppress Th1 Th17 in the intestine. cells also main drivers crescentic glomerulonephritis (GN), most severe form renal autoimmune disease. However, whether Tr1 emerge inflammation and, moreover, they exhibit function during GN have not been thoroughly investigated yet. To address these questions, we used a mouse model experimental double Foxp3mRFP...
The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification new targets to improve therapy a major goal. Growth factors PDGF family their receptors are expressed early in intestinal development found mononuclear cells macrophages adult tissues. Macrophages play distinct role pathogenesis IBD since function crucial maintaining tolerance. We aimed study myeloid expression PDGFR-α mediating homeostasis mouse infectious models. Our results show that...
Abstract Background HMGB1 is a ubiquitously expressed nucleoprotein with proinflammatory functions following cellular release. The protein passively released during tissue necrosis, acting as damage-associated molecular pattern, but can also be actively secreted by immune cells. Stool and serum levels have been suggested markers of both inflammatory bowel disease (IBD) activity colorectal cancer (CRC) invasiveness, antibody-mediated neutralization was beneficial in animal models IBD. We...
Mukosale Heilung ist ein zentrales Therapieziel bei chronisch entzündlicher Darmerkrankung (CED). Dementsprechend spielen Signalwege, die intestinale Entzündung initiieren und aufrecht erhalten, eine entscheidende Rolle der Entwicklung effizienter Therapien. Eine zentrale Funktion mukosaler übernimmt Interleukin 22 (IL-22), welches vermehrt im Darm entzündlichen Darmerkrankungen produziert wird. IL-22 hat aber auch pathogene Eigenschaften kann beispielsweise Entstehung eines Colorektalen...