A5043060790- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- Inflammasome and immune disorders
- Shoulder Injury and Treatment
- Infectious Diseases and Tuberculosis
- Single-cell and spatial transcriptomics
- Hemophilia Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- Amoebic Infections and Treatments
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Immune cells in cancer
- Antioxidant Activity and Oxidative Stress
- Neuroinflammation and Neurodegeneration Mechanisms
- Aldose Reductase and Taurine
- FOXO transcription factor regulation
- Total Knee Arthroplasty Outcomes
- CAR-T cell therapy research
- Metabolism, Diabetes, and Cancer
- Radiology practices and education
- Phagocytosis and Immune Regulation
- Cardiovascular Syncope and Autonomic Disorders
- Knee injuries and reconstruction techniques
- Pancreatic function and diabetes
MRC Protein Phosphorylation and Ubiquitylation Unit
2021-2024
University of Dundee
2021-2024
Cincinnati Children's Hospital Medical Center
2018-2024
Children's Hospital & Medical Center
2024
Medical Research Council
2024
National Institute of Immunology
2017-2023
Jawaharlal Nehru University
2023
University of Delhi
2019
Children’s Institute
2019
University College of Medical Sciences
1999-2015
Aging is associated with changes in circulating levels of various molecules, some which remain undefined. We find that concentrations taurine decline aging mice, monkeys, and humans. A reversal this through supplementation increased the health span (the period healthy living) life mice monkeys. Mechanistically, reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, attenuated inflammaging. In humans, lower correlated...
Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition Th9, Th2, Th17 Foxp3+ regulatory (Treg) produce IL-9. A transcription factor that is critical for IL-9 induction Th9 has not been identified. Here we show the forkhead family Foxo1 required cells. We further inhibition of AKT enhances while it reciprocally regulates IL-17 via Foxo1....
Cytokine storm and sterile inflammation are common features of T cell-mediated autoimmune diseases cell-targeted cancer immunotherapies. Although blocking individual cytokines can mitigate some pathology, the upstream mechanisms governing overabundant innate inflammatory cytokine production remain unknown. Here, we have identified a critical signaling node that is engaged by effector memory cells (TEM) to mobilize broad proinflammatory program in immune system. Cognate interactions between...
Activation of B and T lymphocytes leads to major remodelling the metabolic landscape cells enabling their post-activation functions. However, naive also show differences, genesis, nature functional significance these differences are not yet well understood. Here we that resting B-cells appeared have lower energy demands than T-cells as they consumed levels glucose fatty acids produced less ATP. Resting more dependent on OXPHOS, while dependence aerobic glycolysis. despite an apparently...
Recurrent spontaneous haemarthrosis are commonly seen in patients affected by haemophilia. The knee and the elbow most both amenable to arthroscopic treatment. Arthroscopic synovectomy is indicated after failure of appropriate medical management with recurrent bleeding. Many also demonstrate motion loss functional deterioration. benefits include ability perform adequate synovial debridement, but concomitant lysis adhesion capsular release regain range motion. Results a significant decrease...
Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components immune system might also contribute elicit protective response. Here we have characterized the role T cells offering adult mice infected with JEV. Mice lacking α/β–T (TCRβ–null) highly susceptible and die over 10–18 day period as compared wild-type (WT) which resistant. This is associated high viral...
Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such IL-6, IL-1β, and IL-12, are also associated with rejection organ transplants. However, the pathways immune activation in allogeneic transplantation unclear. While role microbial cell death products has previously described, we identified alloreactive CD4 primary triggers inflammation. Memory engaged MHC II-mismatched dendritic (DCs), leading to production...
OmpU is one of the major porins Vibrio cholerae , a Gram-negative human pathogen. Previously, we showed that stimulates host monocytes and macrophages induces production proinflammatory mediators via activation Toll-like receptor 1/2 (TLR1/2)-MyD88-dependent pathways. In present study, show activates murine dendritic cells (DCs) TLR2-mediated pathway NLRP3 inflammasome, leading to cytokines DC maturation.
Summary Activated T‐cells make both interleukin‐2 (IL2) and its high‐affinity receptor component CD25. Regulatory CD4 (Treg cells) do not IL2, the IL2‐CD25 circuit is considered a paracrine crucial in their generation maintenance. Yet, all are capable of making IL2 at some stage during differentiation, cell‐intrinsic autocrine additionally possible. When we re‐visited experiments with mixed bone marrow chimeras using wide range ratios wild‐type (WT) IL2−/− genotype progenitors, found that,...
Intestinal intraepithelial T lymphocytes (IEL) constitutively express high amounts of the cytotoxic proteases Granzymes (Gzm) A and B are therefore thought to protect intestinal epithelium against infection by killing infected epithelial cells. However, role IEL granzymes in a protective immune response has yet be demonstrated. We show that GzmA GzmB required mice oral, but not intravenous, with Salmonella enterica serovar Typhimurium, consistent an intestine-specific role. IEL-intrinsic...
Abstract We have previously demonstrated co‐receptor level‐associated functional heterogeneity in apparently homogeneous naive peripheral CD 4 T cells, dependent on MHC ‐mediated tonic signals. Maturation pathways can differ between and 8 so we tested whether the latter showed similar heterogeneity. report that, when either polyclonal T‐cell receptor ( TCR )‐transgenic monoclonal cells from young mice were separated into hi lo subsets, responded poorly, but subsets of single‐positive SP )...
Abstract Intraepithelial T lymphocytes (T-IEL) are a large population of cytotoxic cells that protect the small intestinal epithelium against pathogens. Based on ontogeny, T-IEL can be categorized into two major subsets: induced and natural. Natural agonistically selected in thymus self-antigens before migrating directly to intestine. Despite having self-reactive cell antigen receptors (TCR), natural maintained tolerized state gut by unknown mechanisms. We therefore investigated TCR...
Protein synthesis is tightly regulated by both gene-specific and global mechanisms to match the metabolic proliferative demands of cell. While regulation protein in response mitogen or stress signals relatively well understood multiple experimental systems, how different cell types fine-tune their basal rate not known. In a previous study, we showed that resting B T lymphocytes exhibit dramatic differences profile, with implications for post-activation function. Here, show cells, despite...
Memory T and B lymphocyte numbers are thought to be regulated by recent cumulative microbial exposures. We report here that memory-phenotype frequencies in B, CD4 CD8 T-cells 3-monthly serial bleeds from healthy young adult humans were relatively stable over a 1-year period, while Plasmablast not, suggesting environmental exposures affected steady state levels of recently activated but not memory subsets. Frequencies cells correlated, variation them was unlikely determined antigenic...
Abstract Plasma cells (PCs) are terminally differentiated B that secrete protective antibodies and serve as a source of long-term humoral memory. PC precursors appear to be generated late in the germinal center cell response spleen migrate bone marrow (BM) differentiate into PCs. However, developmental molecular mechanisms control generation, migration differentiation long-lived PCs (LLPCs) remain elucidated. In order identify characterize LLPCs we established novel adoptive transfer system....