A5063577714- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Immune Response and Inflammation
- Multiple Sclerosis Research Studies
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Asthma and respiratory diseases
- Systemic Lupus Erythematosus Research
- IL-33, ST2, and ILC Pathways
- Antimicrobial Resistance in Staphylococcus
- Gut microbiota and health
- Immunodeficiency and Autoimmune Disorders
- Platelet Disorders and Treatments
- Heat shock proteins research
- Glycosylation and Glycoproteins Research
- Atherosclerosis and Cardiovascular Diseases
- RNA Interference and Gene Delivery
- Connexins and lens biology
Western University
2016-2025
Yale University
2006-2015
University of Saskatchewan
2008
University of Calgary
2001-2007
University of British Columbia
2005
Abstract Experimental autoimmune encephalomyelitis (EAE) is mediated by inflammatory cells recruited from the circulation to CNS. We used intravital microscopy investigate mechanisms of this recruitment. No leukocyte rolling and very little adhesion was observed in healthy control mice. In contrast, both brain postcapillary venules before onset physical symptoms EAE. Rolling remained elevated for 2 wk returned near normal levels 5 postsymptom onset. Consistent with a role P-selectin...
Abstract Environmental factors strongly influence the development of autoimmune diseases, including multiple sclerosis. Despite this clear association, mechanisms through which environment mediates its effects on disease are poorly understood. Pertussis toxin (PTX) functions as a surrogate for environmental to induce animal models autoimmunity, such experimental encephalomyelitis. Although very little is known about molecular behind function in development, PTX has been hypothesized...
Abstract Lymphocyte CD44 interactions with hyaluronan localized on the endothelium have been demonstrated to mediate rolling and regulate lymphocyte entry into sites of chronic inflammation. Because neutrophils also express CD44, we investigated role in multistep process neutrophil recruitment. CD44−/− wild-type control mice were intrascrotally injected neutrophil-activating chemokine, MIP-2, leukocyte kinetics cremasteric microcirculation 4 h subsequently using intravital microscopy....
Patients with MS have an altered gut microbiota compared to healthy individuals, as well elevated small intestinal permeability, which may be contributing the development and progression of disease.We sought investigate if fecal transplantation was safe tolerable in patients it could improve abnormal permeability.Nine were recruited provided monthly FMTs for up six months. The primary outcome investigated change peripheral blood cytokine concentrations. secondary outcomes composition, safety...
We examined the unique contributions of cytokines IL-21 and IL-4 on germinal center (GC) B cell initiation subsequent maturation in a murine model system. Similar to other reports, we found T follicular helper expression begins prior migration into follicle precedes that IL-4. Consistent with this timing, signaling has greater influence perifollicular pre-GC transition intrafollicular stage. Notably, Bcl6hi cells can form combined absence IL-21R- STAT6-derived signals; however, these nascent...
Staphylococcus aureus is a foremost bacterial pathogen responsible for vast array of human diseases. Staphylococcal superantigens (SAgs) constitute family exotoxins from S. that bind directly to major histocompatibility complex (MHC) class II and T cell receptors drive extensive activation cytokine release. Although these toxins have been implicated in serious disease, including toxic shock syndrome, the specific pathological mechanisms remain unclear. Herein, we aimed elucidate how SAgs...
Signaling occurs between the liver and brain in cholestatic disease, giving rise to sickness behaviors such as fatigue. However, signaling pathways involved are poorly defined. Circulating inflammatory mediator levels increased cholestasis, leading speculation that they may be capable of activating circulating immune cells subsequently could gain access brain. Indeed, we have identified at day 10 after bile duct resection-induced there is activation monocytes express tumor necrosis factor...
Abstract There has been a great deal of interest in adhesion molecules as targets for the treatment multiple sclerosis and other inflammatory diseases. In this study, we systematically evaluate α4 integrin P-selectin therapy murine models sclerosis–for first time directly measuring ability their blockade to inhibit recruitment relate clinical efficacy. Experimental autoimmune encephalomyelitis was induced C57BL/6 or SJL/J mice intravital microscopy used quantify leukocyte interactions within...
To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined earliest stages murine GC B cell differentiation. Peri-follicular precursors first expressed intermediate levels BCL6 while co-expressing transcription factors RelB and IRF4, latter known to repress Bcl6 transcription. Transition BCL6hi follicular state was associated with division, although number required divisions immunogen dose dependent. Potentiating T help or these actively...
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated neutrophils, once extravasated, acquire macrophage-like properties, including potential for immunostimulation MHC class II-mediated antigen...
Immunotherapies for malignant melanoma seek to boost the anti‐tumoral response of CD8 + T cells, but have a limited patient rate, in part due tumoral immune cell infiltration. Genetic or pharmacological inhibition pannexin 1 (PANX1) channel‐forming protein is known decrease tumorigenic properties vitro and ex vivo . Here, we crossed Panx1 knockout ( −/− ) mice with inducible model Braf CA , Pten loxP Tyr::CreER T2 (BPC). We found that deleting gene does not reduce BRAF(V600E)/Pten‐driven...
Abstract B cells have been shown to be phagocytic under some circumstances. However, the capacity of different cell subsets and how this is linked Antigen (Ag) presentation or other functions has not characterized. To address this, we developed 2 µm Ag conjugated bead targets that target pathways including BCR, scavenger, Fc, complement receptors study potential by which phagocytose both cognate non-cognate Ags. We found while follicular B2 (Fo B), marginal zone, B1 are highly BCR-engaging...
We characterized B cell infiltration of the spinal cord in a cell-dependent spontaneous model central nervous system (CNS) autoimmunity that develops proportion mice with mutant T and receptors specific for myelin oligodendrocyte glycoprotein. found that, while males are more likely to develop disease, females have chronic rather than monophasic disease course. was investigated by histology FACs. CD4(+) pervasive throughout white some cases gray matter. cells were almost exclusively...
Generation of specific antibodies during an immune response to infection or vaccination depends on the ability rapidly and accurately select clones antibody-secreting B lymphocytes for expansion. Antigen-specific cell undergo fate decision differentiate into plasma cells, memory germinal center cells. The E26-transformation-specific (ETS) transcription factors Spi-B Spi-C are important regulators development function. is expressed throughout downregulated upon differentiation. highly related...
Abstract Contact sensitivity (CS) is related to delayed-type hypersensitivity and a well-characterized prototype of T cell-mediated inflammation. However, the inflammatory response associated with CS additionally dependent on Ag-specific IgM produced by subpopulation B cells in sensitization. Upon re-exposure hapten, this mediates rapid vascular activation subsequent recruitment proinflammatory local site. Interference pathway prevents full development classic delayed therefore termed “CS...
Prior studies of classical 24 h responses in TNP-Cl (picryl chloride) allergic contact sensitivity (CS), showed mediation by Th1 cells CBA mice, and established that elicitation requires an early 2 CS-initiating component dependent on iNKT cells, IL-4 B-1 B cells. Here, we studied the other form cytotoxic T cell (Tc1) CS DNFB sensitized BALB/c mice determined similar CS-initiation also is required. We systematically tested each step initiation pathway this model. Thus, Tc1 was significantly...
Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. In this study, we investigated the role redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in retinoic acid-related orphan receptor γt+ cells conventional dendritic (DCs) using germline conditional double knockout mice. Although Tmem176a/b appeared surprisingly dispensable for protective function Th17 group 3 innate lymphoid intestinal mucosa, found that they were required DCs...