A5017107725- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Inflammatory Bowel Disease
- Preterm Birth and Chorioamnionitis
- Rheumatoid Arthritis Research and Therapies
- Immunotherapy and Immune Responses
- Dental Education, Practice, Research
- Microscopic Colitis
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Infant Nutrition and Health
- Reproductive System and Pregnancy
- Cell Adhesion Molecules Research
- Neonatal and fetal brain pathology
- Cancer Immunotherapy and Biomarkers
- COVID-19 Impact on Reproduction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Dental Health and Care Utilization
- Neonatal and Maternal Infections
- Advanced Glycation End Products research
- Medical History and Innovations
- Pregnancy and preeclampsia studies
King's College London
2015-2024
Guy's Hospital
2001-2024
King's College - North Carolina
2017
Cancer Research UK
2016
W. L. Gore & Associates (Germany)
2010-2014
Kings Health Partners
2011-2013
National Institute for Health Research
2009-2013
Guy's and St Thomas' NHS Foundation Trust
2009
St Thomas' Hospital
2009
ENT and Allergy
2007
Many body surfaces harbor organ-specific γδ T cell compartments that contribute to tissue integrity. Thus, murine dendritic epidermal cells (DETCs) uniquely expressing receptor (TCR)-Vγ5 chains protect from cutaneous carcinogens. The DETC repertoire is shaped by Skint1, a butyrophilin-like (Btnl) gene expressed specifically thymic epithelial and suprabasal keratinocytes. However, the generality of this mechanism has remained opaque, since neither Skint1 nor DETCs are evolutionarily...
Abstract Objective. Recently, 2 classes of cytokine inhibitors have been defined at the molecular level. The largest group comprises extracellular domains cell surface receptors, and includes both tumor necrosis factor receptors (TNF‐R). present study was conducted to investigate role TNF in arthritis. Methods. We measured p55 p75 soluble TNF‐R (sTNF‐R) serum synovial fluid (SF) samples from patients with rheumatic diseases compared their levels interleukin‐2 (sIL‐2R). Sensitive...
Abstract The biological activity of the pro‐inflammatory cytokine, tumor necrosis factor (TNF)‐α depends on level TNF‐α itself, expression p55 and p75 cell surface receptors for TNF target cells concentrations natural inhibitors TNF‐α, soluble (TNF‐R). Interleukin (IL)‐10 IL‐4 are known to inhibit production by monocytes. We, therefore, investigated effects IL‐10 release TNF‐R human monocytes determine whether these cytokines also indirectly modulated TNF‐α. Exposure (1‐10 U/ml) 24 or 48 h...
Etrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients colon tissues expressed high levels of αE gene (ITGAE) appeared have best response. We compared differences colonic expression ITGAE and other genes between who achieved clinical remission etrolizumab those did.We performed retrospective analysis data collected from 110 UC participated phase 2...
Abstract Bacterial infections are a major cause of mortality in preterm babies, yet our understanding early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very babies (<32 weeks gestation) across episodes invasive bacterial infection (sepsis). We identify dynamically changing signature sepsis, including lymphopenia, reduced dendritic cell...
Acknowledgement of the breadth T-cell pleiotropy has provoked increasing interest in degree to which functional responsiveness is elicited by environmental cues versus differentiation. This particularly relevant for young animals requiring rapid responses acute exposure. In mice, gammadelta T cells are disproportionately important immuno-protection. To examine situation humans, we compared populations and clones from term preterm babies, adults. By comparison with alphabeta cells,...
Abstract The RGS1 gene is associated with celiac disease, multiple sclerosis, and type I diabetes, which are all T cell-mediated pathologies, yet there no reported analysis of regulator G protein signaling (RGS)1 biology in human cells. This study shows that expression substantially higher cells from gut versus peripheral blood this can be exaggerated intestinal inflammation. Elevated levels profoundly reduce cell migration to lymphoid-homing chemokines, whereas depletion selectively...
The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, understanding largely derived from animal model data. Defining this phenotype in samples important UC pathogenesis and translational importance therapeutic targeting αEβ7–E-cadherin interactions. αEβ7+ αEβ7− colonic cell...
We have previously hypothesized that the pro-inflammatory cytokine TNF alpha has a pivotal role in pathogenesis of rheumatoid arthritis (RA). It mediates its effects by cross-linking surface p55 receptors (TNF-R), which can be proteolytically cleaved to yield soluble fragments. Upon binding TNF-R (sTNF-R) inhibit function. investigated enzymatic nature proteases involved cleavage, and found this process is blocked synthetic inhibitor matrix metallo-proteinase activity (MMP), BB-2275....
Abstract We previously proposed the hypothesis that pro‐inflammatory cytokine tumor necrosis factor‐α (TNF‐α) plays a pivotal role in pathogenesis of rheumatoid arthritis (RA) based on our observations it is dominant inducer interleukin‐1 (IL‐1) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) production RA synovial joint mononuclear (MNC) cells culture. Since TNF‐α acts via two membrane receptors, we have extended those studies to investigate distribution p55 p75 TNF receptors...
Abstract Infection and infection-related complications are important causes of death morbidity following preterm birth. Despite this risk, there is limited understanding the development immune system in those born prematurely, how influenced by perinatal factors. Here we prospectively longitudinally follow a cohort babies before 32 weeks gestation. We demonstrate that babies, including extremely prematurely (<28 weeks), capable rapidly acquiring some adult levels functionality, which...
Intestinal homeostasis is maintained by the response of gut-associated lymphoid tissue to bacteria transported across follicle associated epithelium into subepithelial dome. The initial antigens and how are handled incompletely understood. By iterative application spatial transcriptomics multiplexed single-cell technologies, we identify that double negative 2 subset B cells, previously with autoimmune diseases, present in dome health. We show this location cells interact dendritic...
The role of the receptor for advanced glycation end products (RAGE) in promoting inflammatory response through activation NF-κB pathway is well established. Recent findings indicate that RAGE may also have a regulative function apoptosis, as cellular proliferation, differentiation, and adhesion. Unlike other organs, lung tissue adulthood during organ development shows relatively high levels expression. Thus organogenesis homeostasis be proposed. To evaluate adult homeostasis, we generated...
Abstract We recently demonstrated that the major effector function of neonatal CD4+ T cells is to produce CXCL8, a prototypic cytokine innate immune cells. In this article, we show CXCL8 expression, prior proliferation, common in newly arising (so-called “recent thymic emigrants”) adults, as well babies. This potential acquired human thymus, TCR signaling, but rather than describing end-stage differentiation, such cells, whether isolated from neonates or can further differentiate into...
Abstract Introduction Infection and inflammation have been implicated in the etiology subsequent morbidity associated with preterm birth. At present, there are no tests to assess for fetal compartment infection. The thymus, a gland integral immune system, has shown involute animal models of antenatal infection, but its response human fetuses not studied. This study aims: (a) generate magnetic resonance imaging (MRI) ‐derived thymus volumes standardized weight; (b) compare from that delivered...
We have proposed the hypothesis that tumour necrosis factor α (TNF‐α) has a pivotal role in pathogenesis of rheumatoid arthritis, based on vitro observations RA synovial joint cell cultures removal TNF‐α, inhibited other potentially pathogenic cytokines such as equally pro‐inflammatory cytokine interleukin 1 (IL‐I) and macrophage activating factor, GM‐CSF. Here we describe both (RA) osteoarthritic (OA) there is homeostatic mechanism to regulate activities TNF‐α. This concept several...
Abstract A critical event in B cell immortilization by Epstein‐Barr virus (EBV) is the establishment of an autocrine loop where cells produce a growth factor which supports their own proliferation. We investigated potential lymphoblastoid lines (LCL) and Burkitt lymphoma (BL) to respond cytotoxins, tumor necrosis factor‐α (TNF‐α) lymphotoxin (LT). Transformation vitro peripheral blood EBV from seven different donors resulted spontaneous production both LT (11542 pg/ml ± 7546, mean SD) and,...