Background And Objectives: B cell depleting anti-CD20 monoclonal antibodies (aCD20 mAbs) are highly effective in treatment of multiple sclerosis (MS) but fail to halt the formation of meningeal ectopic lymphoid tissue (mELT) in the murine model experimental autoimmune encephalomyelitis (EAE). While mELT can be examined in EAE, it is not accessible in MS patients. Our key objectives were to compare the immune cells in cerebrospinal fluid (CSF), which is accessible in patients, with those in mELT, and to study the effects of aCD20 mAbs on CSF and mELT in EAE.
View Article and Find Full Text PDFBackground And Objectives: The factors that drive progression in multiple sclerosis (MS) remain obscure. Identification of key properties of meningeal inflammation will contribute to a better understanding of the mechanisms of progression and how to prevent it.
Methods: Applying single-cell RNA sequencing, we compared gene expression profiles in immune cells from meningeal ectopic lymphoid tissue (mELT) with those from secondary lymphoid organs (SLOs) in spontaneous chronic experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
Mol Aspects Med
August 2023
The gram-negative bacterium Helicobacter pylori is the most common chronic bacterial infection and the main cause of gastric cancer. Due to the increasing antimicrobial resistance of H. pylori, the development of an efficacious vaccine is a valid option to protect from disease or infection and ultimately prevent gastric cancer.
View Article and Find Full Text PDFBackground & Aims: Infection with Helicobacter pylori strongly affects global health by causing chronic gastritis, ulcer disease, and gastric cancer. Although extensive research into the strong immune response against this persistently colonizing bacterium exists, the specific role of CD8 T cells remains elusive.
Methods: We comprehensively characterize gastric H pylori-specific CD8 T-cell responses in mice and humans by flow cytometry, RNA-sequencing, immunohistochemistry, and ChipCytometry, applying functional analyses including T-cell depletion, H pylori eradication, and ex vivo restimulation.
Colorectal cancer is one of the most common cancers and a major cause of mortality. Proinflammatory and antitumor immune responses play critical roles in colitis-associated colon cancer. CCL17, a chemokine of the C-C family and ligand for CCR4, is expressed by intestinal dendritic cells in the steady state and is upregulated during colitis in mouse models and inflammatory bowel disease patients.
View Article and Find Full Text PDFIntroduction: In spite of antiviral treatment, herpes simplex encephalitis (HSE) remains associated with a poor prognosis and often results in neurological impairment. The B cell response in HSE is poorly understood. The objective of this study was to identify, in a patient with HSE, B cell clones in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs) that expanded between two different time points during the course of infection.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
January 2022
Background And Objectives: To investigate whether the formation or retention of meningeal ectopic lymphoid tissue (mELT) can be inhibited by the sphingosine 1-phosphate receptor 1,5 modulator siponimod (BAF312) in a murine model of multiple sclerosis (MS).
Methods: A murine spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model, featuring meningeal inflammatory infiltrates resembling those in MS, was used. To prevent or treat EAE, siponimod was administered daily starting either before EAE onset or at peak of disease.
Objective: To investigate whether anti-CD20 B-cell-depleting monoclonal antibodies (ɑCD20 mAbs) inhibit the formation or retention of meningeal ectopic lymphoid tissue (mELT) in a murine model of multiple sclerosis (MS).
Methods: We used a spontaneous chronic experimental autoimmune encephalomyelitis (EAE) model of mice with mutant T-cell and B-cell receptors specific for myelin oligodendrocyte glycoprotein (MOG), which develop meningeal inflammatory infiltrates resembling those described in MS. ɑCD20 mAbs were administered in either a preventive or a treatment regimen.
Gut microbiota and the immune system are in constant exchange shaping both host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40-CD40L axis showed promising results as these molecules are deregulated in certain IBD patients.
View Article and Find Full Text PDFIntestinal integrity is maintained by balanced numbers of CD103+ Dendritic cells (DCs), which generate peripherally induced regulatory T cells (iTregs). We have developed a mouse model where DC-specific constitutive CD40 signals caused a strong reduction of CD103+ DCs in the lamina propria (LP) and intestinal lymph nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic mice on the C57Bl/6-background (B6) developed fatal colitis.
View Article and Find Full Text PDFEvidence based public health requires knowledge about successful dissemination of public health measures. This study analyses (a) the changes in worksite tobacco prevention (TP) in the Canton of Zurich, Switzerland, between 2007 and 2009; (b1) the results of a multistep versus a "brochure only" dissemination strategy; (b2) the results of a monothematic versus a comprehensive dissemination strategy that aim to get companies to adopt TP measures; and (c) whether worksite TP is associated with health-related outcomes. A longitudinal design with randomized control groups was applied.
View Article and Find Full Text PDFObjectives: This study provides information about the prevalence of tobacco prevention (TP) and the stages of change with respect to the introduction of TP among companies in the Canton of Zurich (n = 1,648). It explores the factors that predict restrictiveness of smoking policies, number of individual support measures, interest in services to promote TP, and the relationship between TP and health outcomes.
Methods: Data were gathered by means of a written questionnaire and analysed using ordinal regression models.