A5017577290- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Heat shock proteins research
- Immune Cell Function and Interaction
- Exercise and Physiological Responses
- CAR-T cell therapy research
- Immune Response and Inflammation
- Endoplasmic Reticulum Stress and Disease
- Dermatology and Skin Diseases
- Trace Elements in Health
- Asthma and respiratory diseases
- vaccines and immunoinformatics approaches
- Toxin Mechanisms and Immunotoxins
- Cancer Immunotherapy and Biomarkers
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects of Natural Compounds
- Chemokine receptors and signaling
- Antimicrobial Peptides and Activities
- Immunodeficiency and Autoimmune Disorders
- Phagocytosis and Immune Regulation
- Osteoarthritis Treatment and Mechanisms
- Immune cells in cancer
- Bee Products Chemical Analysis
Newcastle University
2016-2019
NIHR Newcastle Biomedical Research Centre
2017-2019
Newcastle upon Tyne Hospitals NHS Foundation Trust
2017-2019
Versus Arthritis
2017-2019
Utrecht University
2007-2015
La Jolla Institute for Immunology
2015
Osteoarthritis (OA) is a leading cause of disability, globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target therapeutically have had limited success. A better understanding the cellular and molecular processes occurring synovium needed develop novel therapeutics. We investigated macrophage phenotype gene expression tissue inflammatory-arthritis (IA) patients. Compared with IA, contained higher but variable proportions macrophages (P < 0.001)....
Until recently, the immune system was seen solely as a defense with its primary task being elimination of unwanted microbial invaders. Currently, however, functional significance has obtained much wider perspective, to include among others maintenance and restoration homeostasis following tissue damage. In this latter aspect, there is growing interest in identification molecules involved, such so-called danger or damage-associated molecular patterns (DAMPs), also called alarmins. Since heat...
Stress proteins, such as members of the heat-shock protein (HSP) family, are up-regulated by cells in inflamed tissue and can be viewed functionally "biomarkers" for immune system to monitor inflammation. Exogenous administration stress proteins has induced immunoregulation various models inflammation also been shown effective clinical trials humans. This study was undertaken test hypothesis that boosting endogenous HSP expression restore through T specific proteins.Stress manipulated vivo...
Previous studies in mouse models of autoimmune diabetes and encephalomyelitis have indicated that the selective delivery self-antigen to endocytic receptor DEC205 on steady-state dendritic cells (DCs) may represent a suitable approach induce Ag-specific immune tolerance. In this study, we aimed examine whether DEC205(+) DC targeting single immunodominant peptide derived from human cartilage proteoglycan (PG) can promote tolerance PG-induced arthritis (PGIA). Besides disease induction by...
Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety autoimmune and allergic diseases as well post-transplant complications. Nevertheless, current manufacturing Tregs a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons results studies performed. While number clinical trials testing is already substantial, it seems to be crucial provide some standardised characteristics Treg...
Cellular therapies with tolerogenic antigen-presenting cells (tolAPC) show great promise for the treatment of autoimmune diseases and prevention destructive immune responses after transplantation. The methodologies generating tolAPC vary greatly between different laboratories, making it difficult to compare data from studies; thus constituting a major hurdle development standardised therapeutic products. Here we describe an initiative by members field generate minimum information model...
Tolerogenic dendritic cells (tolDCs) are a promising treatment modality for diseases caused by breach in immune tolerance, such as rheumatoid arthritis. Current medication these is directed towards symptom suppression but no real cure available yet. TolDC-based therapy aims to restore tolerance an antigen-specific manner. Here we used mouse model address two major questions: i) maturation stimulus needed tolDC function vitro and vivo required functioning experimental arthritis ii) can tolDCs...
Previously, it has been shown that heat shock protein 70 (HSP70) can prevent inflammatory damage in experimental autoimmune disease models. Various possible underlying working mechanisms have proposed. One possibility is HSP70 induces a tolerogenic phenotype dendritic cells (DCs) as result of the direct interaction antigen with DC. Tolerogenic DCs induce antigen-specific regulatory T and dampen pathogenic cell responses. We show treatment murine either mycobacterial (Mt) or mouse pulsed...
Autologous tolerogenic dendritic cells (tolDC) are a promising therapeutic strategy for inflammatory arthritis (IA) as they can regulate autoantigen-specific T cell responses. Here, we investigated two outstanding priorities clinical development: (i) the suitability of using heat-shock proteins (HSP), abundant in inflamed synovia, surrogate autoantigens to be presented by tolDC and (ii) identification functional biomarkers that confirm regulatory activity.Cell proliferation dye-labelled...
Exposure to environmental toxicants can alter a range of cellular functions involved in the immune response. Increased expression stress protein metallothionein 1 (MT1) is one example hereof. Previously, it has been reported that MT1 several immunosuppressive properties. Furthermore, we earlier showed functionally tolerogenic dendritic cells (DCs) expressed increased mRNA levels MT1. Here, demonstrate dexamethasone-treated murine DCs are and produce However, these do not actively transport...
Tolerogenic dendritic cells (DCs) can induce regulatory T and dampen pathogenic cell responses. Therefore, they are possible therapeutic targets in autoimmune diseases. In this study we investigated whether mouse tolerogenic DCs induced by the phytonutrient carvacrol, a molecule with known anti-inflammatory properties, combination physiological stress. We show that treatment of carvacrol thermal stress led to mRNA expression both pro- mediators. Interestingly, treated mixed gene profile had...
Abstract THEMIS is required for setting the threshold conventional selection of thymocytes by dampening TCR signals, resulting in accumulation “naïve” T cells periphery. In contrast, agonist selection, which an alternative way to induce self tolerance, requires strong signals and does not involve regulation THEMIS. Using OVA-specific monoclonal MHC class II restricted DO11.10 transgenic system, we found that many are selected along path appear as co-receptor double negative (DN) TCRab...