A5058161705- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Trace Elements in Health
- Cancer, Hypoxia, and Metabolism
- Spectroscopy Techniques in Biomedical and Chemical Research
- Hematopoietic Stem Cell Transplantation
- Immunodeficiency and Autoimmune Disorders
- Advanced biosensing and bioanalysis techniques
- Viral gastroenteritis research and epidemiology
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Drug-Induced Hepatotoxicity and Protection
- Bioactive Compounds and Antitumor Agents
- Invertebrate Immune Response Mechanisms
- PARP inhibition in cancer therapy
- Renal cell carcinoma treatment
- Adrenal Hormones and Disorders
- Mechanisms of cancer metastasis
- Genomics, phytochemicals, and oxidative stress
- Metabolomics and Mass Spectrometry Studies
- Cancer Mechanisms and Therapy
- interferon and immune responses
- Viral Infections and Immunology Research
MRC Human Immunology Unit
2016-2024
University of Oxford
2016-2024
Centre for Human Genetics
2024
Medical Research Council
2016-2020
Indian Institute of Science Bangalore
2010-2017
Significance Cellular metabolism is tightly regulated by AMP-activated protein kinase (AMPK): the function of which influenced folliculin (FLCN), folliculin-interacting (FNIP)1, and FNIP2. FLCN a known tumor-suppressor that mutated in Birt–Hogg–Dubé syndrome, whereas FNIP1 FNIP2 are binding partners FLCN. Previous reports have suggested FLCN/FNIP1/FNIP2 complex acts positive regulator AMPK, other suggest opposite. Using new mouse model deficiency, our findings support latter: we found...
Developing B cells can be positively or negatively selected by self-antigens, but the mechanisms that determine these outcomes are incompletely understood. Here, we show a cell intrinsic switch between positive and negative selection during ontogeny is determined change from Lin28b to let-7 gene expression. Ectopic expression of transgene in murine restored autoreactive B-1 self-antigen adult bone marrow. Analysis antigen-specific immature early late identified Lin28b-dependent genes...
Thymic atrophy is known to occur during infections; however, there limited understanding of its causes and the cross-talk between different pathways. This study investigates mechanisms involved in thymic a model oral infection by Salmonella enterica serovar Typhimurium (S. typhimurium). Significant death CD4(+) CD8(+) thymocytes, but not single-positive thymocytes or peripheral lymphocytes, observed at later stages with live, heat-killed, bacteria. The Fas-independent as shown studies lpr...
Acetaminophen is a widely prescribed drug used to relieve pain and fever; however, it leading cause of drug-induced liver injury burden on public healthcare. In this study, hepatotoxicity in mice post oral dosing acetaminophen was investigated using sera samples with Fourier Transform Infrared microspectroscopy. The infrared spectra treated livers BALB/c show decrease glycogen, increase amounts cholesteryl esters DNA respectively. Rescue experiments L-methionine demonstrate that depletion...
Background. Interferon γ (IFN-γ) increases the expression of multiple genes and responses; however, mechanisms by which IFN-γ downmodulates cellular responses is not well understood. In this study, repression CCL3 CCL4 nitric oxide synthase 2 (NOS2) in macrophages upon Salmonella typhimurium infection mice was investigated. Methods. Small molecule regulators adherent peritoneal exudates cells (A-PECs) from Nos2−/−mice were used to identify contribution signaling molecules during...
Abstract The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, oral infection mice with Salmonella Typhimurium ( S . Typhimurium). major highlights are: First, block the developmental pathway CD4 − CD8 double negative (DN) thymocytes observed. Second, + positive (DP) thymocytes, mainly DP1 (CD5 lo CD3 ) and DP2 hi int ), but DP3 subsets are...
Sepsis is a life threatening condition resulting from high burden of infection. It major health care problem and associated with inflammation, organ dysfunction significant mortality. However, proper understanding delineating the changes that occur during this complex remains challenge. A comparative study involving intra-peritoneal injection BALB/c mice Salmonella Typhimurium (infection), lipopolysaccharide (endotoxic shock) or thioglycollate (sterile peritonitis) was performed. The in...
Dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome is characterized by a failure the germinal center response, process involving proliferation and positive selection antigen-specific B cells. Here, we describe how DOCK8-deficient cells are blocked at light-zone checkpoint in centers immunized mice, where they unable to respond T cell–dependent survival signals consequently differentiate into plasma or memory Although can acquire present antigen initiate activation cognate cells,...
Interferon-gamma (Ifnγ), a key macrophage activating cytokine, plays pleiotropic roles in host immunity. In this study, the ability of Ifnγ to induce aggregation resident mouse adherent peritoneal exudate cells (APECs), consisting primarily macrophages, was investigated. Cell-cell interactions involve adhesion molecules and, upon addition Ifnγ, CD11b re-localizes preferentially sites interaction on APECs. A functional role enhancing is demonstrated using Reopro, blocking reagent, and siRNA...
Thymic atrophy, due to the depletion of CD4(+) CD8(+) thymocytes, is observed during infections with numerous pathogens. Several mechanisms, such as glucocorticoids and inflammatory cytokines, are known be involved in this process; however, roles intracellular signaling molecules have not been investigated. In study, functional role c-Jun NH2 -terminal kinase (JNK) infection-induced thymic atrophy was addressed. The levels phosphorylated JNK immature thymocytes from C57BL/6 (Nramp-deficient)...
Prolidase deficiency (PD) is a multisystem disorder caused by mutations in the PEPD gene, which encodes ubiquitously expressed metallopeptidase essential for hydrolysis of dipeptides containing C-terminal proline or hydroxyproline. PD typically presents childhood with developmental delay, skin ulcers, recurrent infections, and, some patients, autoimmune features that can mimic systemic lupus erythematosus. The basis association uncertain, but might be due to self-antigen exposure tissue...
Abstract Peripheral tolerance prevents the initiation of damaging immune responses by autoreactive lymphocytes. While tolerogenic mechanisms are tightly regulated antigen-dependent and independent signals, downstream pathways incompletely understood. N-myc downstream-regulated gene 1 (NDRG1), an anti-cancer therapeutic target, has previously been implicated as a CD4 + T cell clonal anergy factor. By RNA-sequencing, we identified Ndrg1 third most upregulated in anergic, compared to naïve...
B-lymphocyte development and selection is central to adaptive immunity self-tolerance. These processes require B cell receptor (BCR)-signaling occur in bone marrow, an environment with variable hypoxia, but whether Hypoxia-inducible factor (HIF) involved unknown. We show high HIF-activity human marrow pro/preB cells that decreased at the immature stage. Stage-specific HIF-suppression was required for development, since constitutive HIF-1α-activation murine led developmental-arrest, limited...