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Deputy Director MRC-UCL Centre for Medical Molecular Virology ... In 2014 two of these studies were published in Nature.
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9.00-9.30am Registration 9.30-9.35am Professor Hans Stauss
Professor David Abraham Professor of Cell and Molecular Biology Head of Research Department of Inflammation Director of Centre for Rheumatology and Connective Tissue Diseases, UCL Division of Medicine KTE Champion, UCL Faculty of Medical Sciences Professor Judith Breuer Professor of Virology, UCL Division of Infection & Immunity Deputy Director MRC-UCL Centre for Medical Molecular Virology Honorary Consultant Virologist, Great Ormond Street Hospital and Head of UCL VZV Reference Laboratory Professor Arne Akbar Professor of Immunology UCL Division of Infection & Immunity Professor Michael Ehrenstein Chair, Infection, Immunity and Inflammation Symposium Organising Committee, UCL Personalised Medicine Domain Professor of Experimental Rheumatology UCL Division of Medicine Cassie Harley-Boyce Communications and Events Officer Research Coordination Office Office of the Vice-Provost (Health) UCL School of Life and Medical Sciences
Professor Hans Stauss UCLPartners Programme Director for Infection, Immunity and Inflammation and Immunology and Transplantation Academic Director, UCL Institute of Immunity and Transplantation Co-director, UCL Division of Infection & Immunity Head of UCL Research Department of Immunology Head of Clinical Immunology, UCL Royal Free Campus Professor Adrian Thrasher Professor of Paediatric Immunology Wellcome Trust Principal Research Fellow Programme Head of Infection, Immunity, Inflammation and Physiological Medicine Academic Programme UCL Institute of Child Health Dr Mahdad Noursadeghi Senior Lecturer UCL Division of Infection & Immunity
Professor Lucy Walker Chair in Immune Regulation Research Department of Immunology UCL Division of Infection & Immunity David Wiseman Research Coordinator - Infection, Immunology and Inflammation Research Coordination Office Office of the Vice-Provost (Health) UCL School of Life and Medical Sciences
Dr Emma C Morris Reader in Immunology, UCL Institute of Immunity and Transplantation Consultant Haematologist (BMT), Royal Free Hospital and University College London Hospital UCLH/UCL NIHR BRC Programme Director (Infection, Immunity and Inflammation) NIHR University College London Hospitals Biomedical Research Centre Infection, Immunity and Inflammation Programme Our Biomedical Research Centre (BRC) is the result of an outstanding partnership between University College London Hospitals NHS Foundation Trust (UCLH) and UCL. The BRC provides essential clinical research infrastructure across UCLH and UCL on which world leading Programmes of research are being developed. The BRC infrastructure enables UCLH/UCL to take innovations in basic science and turn them into novel therapies and devices, diagnostic tests or validated predictive markers, which may have a direct effect on patients. The ultimate aim is to advance experimental medicine and save lives. The BRC specifically supports experimental medicine research with a focus on ‘first in man’ clinical trials. The BRC consists of four Programmes of world class strength – Cancer, Neuroscience, Cardiometabolic and Infection, Immunity and Inflammation (or III). The Infection, Immunity and Inflammation (III) Programme currently has five strategic priority areas: fibrosis and inflammation gene and cell therapy for cancer, infection and immune disorders new therapies for inflammatory arthritis-rheumatology infectious disease prediction and stratification novel therapies for protein folding disorders. The BRC’s III Programme is leading on two national BioResource initiatives: The HIV Bioresource linked to the UK Collaborative HIC Cohort Study (UK CHIC) (www.ucl.ac.uk/iph/research/hivbiostatistics/CHIC) BioAID, a multicentre transcriptome profiling project linking UCLH/UCL, Imperial- Hammersmith, Imperial-St Marys, GSTT/KCL, Cambridge University Hospitals NHS Trust-Addenbrookes and Oxford University Hospitals NHS Trust-John Radcliffe Hospital. To encourage patients and the public to get actively involved in our research and to support researchers in involving lay people, the III Programme has a patient panel. This panel looks at research proposals and study documentation and advises researchers.
Chair: Professor Michael Ehrenstein Professor of Experimental Rheumatology UCL Division of Medicine Michael Ehrenstein is Professor of Experimental Rheumatology at UCL and Honorary Consultant Rheumatologist at University College London Hospitals (UCLH). His research group’s objectives are to use biologic therapy as a molecular scalpel to understand pathogenesis of autoimmune rheumatic disease (including rheumatoid arthritis and systemic lupus erythematosus) both in terms of loss of immune tolerance and ongoing inflammation, to elucidate the basis for adverse effects to biologic therapies, to develop novel (and safer) therapies, to improve existing therapies, and to target therapies to patients most likely to respond including developing biomarkers of response.
Professor Claudia Mauri Professor of Immunology UCL Division of Medicine Microbiota, regulatory B cells and arthritis: insight into a new mechanism of regulation Claudia Mauri received her PhD (equivalent) magna cum laude degree in 1992 from the University La Sapienza in Rome. She worked as Postdoctoral Fellow at The Kennedy Institute of Rheumatology. She then moved to UCL in 2002 where she has established her group. She is Professor of Immunology and the new Champion for Women. Her research interest is understanding the mechanisms driving autoimmunity with a particular interest in understanding B cell regulation in experimental models of rheumatic disease and in patients with Systemic Lupus Erythematous and rheumatoid arthritis.
Chair: Professor Arne N. Akbar - Professor of Immunology, UCL Division of Infection & Immunity Professor Akbar is internationally recognised for his studies on mechanisms that control the differentiation and senescence of human T lymphocytes. In 2014 two of these studies were published in Nature Immunology and the Journal of Clinical Investigation (his H factor is 51). In addition, he has made seminal observations about how different CD45R isoforms can be used to discriminate between primed and T cells and these markers are now used in routine diagnostic practice. Furthermore, his group was one of the first to identify human regulatory T cells. He was also closely involved in the development of Basilizximab (Simulect), used for the prevention of acute solid organ graft rejection (Akbar is a joint patent holder) that has been used to treat ~300,000 patients and generated £24 million in royalty income to UCL. His group have also developed cutaneous recall antigen challenge models in humans for the study of immunity in vivo that have been adopted by researchers worldwide and by GlaxoSmithKlein. His research group consists of basic scientists and clinicians facilitating the translational aspects of his work. The benefit of this combination is exemplified by the recent award of an MRC Experimental Medicine Grant (Akbar PI; £3.2 million) to investigate whether blocking p38MAP kinase in older humans in vivo enhances their responses to recall antigen challenge in the skin. His work involves studies at the interface between academia, industry and clinical practice. Dr Matthew C Gage - Research Associate, UCL Centre for Clinical Pharmacology, Metabolism & Experimental Therapeutics Inflammasome-processed interleukin-18 levels are negatively regulated by lipid-activated nuclear receptor LXR through multiple mechanisms Authors: Gage MC, Pourcet B, Leon T, Valledor AF, Pineda-Torra I IL-18 is a member of the IL-1 family; central mediators of innate immunity and inflammation which are tightly regulated to ensure a balance between amplification of innate immunity and uncontrolled inflammation. IL-18 is primarily secreted by macrophages and dendritic cells, induces interferon gamma (IFNγ) production by Th1 cells and is thus considered a pro- inflammatory cytokine. IL-18 is involved in multiple diseases including psoriasis, emphysema, myocardial dysfunction, metabolic syndrome, atherosclerosis and several autoimmune diseases yet relatively little is known regarding its regulation. Ligand-activated nuclear receptors LXRs are crucial regulators of macrophage cholesterol homeostasis as well as macrophage inflammatory responses, phagocytosis and apoptosis. Here, we show that LXRs are negative regulators of LPS-induced mRNA and protein expression of IL-18 in bone marrow-derived macrophages. This regulation is specific since it is abolished both in the presence of a specific LXR antagonist or in macrophages from LXR-deficient mice. IL-18 is expressed as a pro-IL-18 protein, which is processed by inflammasome-activated caspase 1. In addition to IL-18 transcriptional regulation, IL-18 maturation is inhibited by LXR activation through negative regulation of caspase 1 expression and activation. Finally, the expression of IL-18BP, a potent endogenous inhibitor of IL- 18, is indirectly induced by LXR ligand activation via the hematopoietic transcription factor IRF8, thus identifying IL-18BP as a novel IRF8 target gene. In conclusion, LXR activation inhibits IL- levels through regulation of its transcription and maturation into an active pro-inflammatory cytokine. Regulation of IL-18 levels by LXR could be important for the modulation of various metabolic and inflammatory disorders.
James Heather - PhD Researcher, Innate2Adaptive lab, UCL Division of Infection & Immunity Idiosyncratic perturbations of the T cell receptor population structure in HIV infection Authors: Heather JM, Best K, Oakes T, Roe J, Gray ER, Thomas N, Noursadeghi M, Chain B Global analysis of the T cell receptor (TCR) repertoire reveals the population structure of the T cell compartment, which reflects the immunological history of the individual. In this study we analyse the TCR repertoires of a cohort of treatment naïve HIV-infected individuals before and after commencement of antiretroviral therapy, and compare them to repertoires of healthy volunteers. We develop a protocol for deep-sequencing TCR transcripts, which includes molecular barcoding and error-correction to generate robust quantitative repertoire data. The TCR repertoires of HIV+ individuals are highly perturbed, with expansion of private, low-frequency clones driving the formation of highly divergent repertoires with very low clonal diversity. The decrease in clonal diversity is correlated with CD8+, but not CD4+ cell counts. V and J TCR gene usage and complementarity determining region 3 (CDR3) profiles of patients are divergent both from healthy controls and from each other, reflecting an idiosyncratic response to HIV infection. Introduction of effective antiretroviral therapy (ART) partially reversed the clonal inequality caused by large clonal expansions, yet repertoire complexity remained low. During treatment the frequency of several HIV-associated CDR3s decreased, while CMV- and EBV-associated CDR frequencies increased. HIV infection was also associated with a deficiency in mucosal-associated invariant T cell alpha chains, a deficit which did not recover on treatment. Our observations support a model in which chronic HIV infection simultaneously drives depletion of the CD4+ T cell compartment and concomitant expansion of the CD8+ compartment. Both aspects of repertoire dysregulation may disturb normal immune homeostasis and contribute to AIDS pathogenesis. Dr Julia Kenny - Senior Clinical Research Fellow, Infection, Immunity, Inflammation and Physiology, UCL Institute of Child Health Structural cardiovascular changes are reversible in HIV-infected children in Zambia and Uganda Authors: Kenny J, Cook A, Mirembe G, Masaku D, Wavamunno P, Odongo F, Rapala A, Deanfield J, Gibb D, Klein N Background - Carotid intimal medial thickness (IMT) and pulse wave velocity (PWV), measures of cardiovascular structure/function, are impaired in HIV-infected children in high-income countries. Few longitudinal data are available: none come from Africa where 90% HIV-infected children live. Methods - ART-naïve and virologically suppressed ART-experienced HIV-infected children had IMT and PWV measured at baseline, 48 and 96 weeks. Age-matched HIV-uninfected controls had a single assessment. Baseline differences between ART-naïve/experienced children vs controls, and longitudinal changes in HIV-infected children were compared. Results - In 208 ART-naïve children with median age 2.9y(IQR 1.7–4.4) and 209 HIV-uninfected controls median age 3.0y(2.1–4.1), mean(sd) cIMT was 0.46(0.04) v 0.44(0.04)mm (p=0.0001); PWV was 5.85(0.8) vs 5.67(0.74)m/sec (p=0.04). Among 74 ART-experienced children on ART for mean 3.7y, median age 6.9y(5.9–8.50) and 75 uninfected controls, median age 6.7y(5.6-8.6), mean(sd) cIMT was 0.46(0.05) vs 0.45(0.04)mm (p=0.09); PWV was 5.63(0.61) vs 5.69(0.69)m/s (p=0.57). In ART naïve children IMT and PWV significantly decreased from baseline (ART
functional antigen specific class CD4+ T cells. However due to the absence of CD8 co-receptors, class I restricted CD4+ T cells recognize MHC-I presented ligands with reduced avidity. To increase surface expression of the introduced TCR and thus improve the functional avidity of class I restricted CD4+ T cells, additional CD3 molecules plus class I restricted F5-TCR were co- transduced into murine CD4+ T cells. Co-transduction of F5-TCR and CD3 into CD4+ T cells led to enhanced surface expression of the F5-TCR and enhanced cytokine production and proliferation responses in vitro. F5-TCR-CD3 CD4+ T cells transferred into irradiated tumour bearing syngeneic recipients demonstrated greater expansion, persistence and faster trafficking to the tumour site than F5-TCR only CD4+ T cells. F5-TCR-CD3 CD4+ T cells demonstrated superior control of tumour growth. This however did not translate into a survival benefit as mice that received adoptive transfer of F5-TCR-CD3 CD4+ T cells developed marked toxicity. This autoimmune pathology was not mediated by mispairing of the introduced TCR: transfer of CD alone in the absence of additional TCR was sufficient to increase the expression of the endogenous TCR repertoire and cause auto-immune toxicity of CD4+ T cells, Co-transfer of CD plus F5-TCR in CD8+ T cells did not lead to toxicity in vivo. Efficient tumour immunity without toxicity was achieved by TCR plus CD3 gene transfer into ‘mono-clonal’ transgenic CD4+ T cells. Dr Jimstan Periselneris - Clinical Research Fellow, UCL Centre for Inflammation & Tissue Repair The inflammatory response to Streptococcus pneumoniae is exaggerated by the polysaccharide capsule Authors: Periselneris J N, Chimalapati S, Tomlinson G, Hyams C, Dyson S, Singer M, Noursadeghi M, Brown J S The inflammatory response to bacteria requires the interaction of pattern recognition receptors with bacterial surface constituents. Streptococcus pneumoniae has a polysaccharide capsule that is an essential virulence factor that would be expected to inhibit host / pathogen interactions, thereby reducing inflammatory responses. We tested this hypothesis by characterising the effect of S. pneumoniae capsule on the inflammatory response using the S. pneumoniae TIGR4 strain and its unencapsulated derivative TIGR4cps. Despite being more sensitive to phagocytosis by human monocyte derived macrophages than TIGR4, RNA transcripts and supernatant levels of TNF, IL1β, and IL6 were reduced in response to infection with TIGR4cps. Furthermore, TIGR generated greater neutrophilic infiltrate in a mouse model of pneumonia, and greater physiological derangement in a rat sepsis model than TIGR4cps. Whole genome transcriptome analysis demonstrated that there was a generally reduced pro-inflammatory response to the TIGR4cps strain compared to the TIGR4 strain. Notably, preventing phagocytosis preserved the difference in inflammatory response between the strains. Additional in vitro experiments excluded differences in TLR2 signalling, antibody recognition, the inflammasome, and lectin-mediated signalling as mechanisms driving differences in inflammatory responses between TIGR4 and Δcps. However a transcription factor array suggested that TIGR4cps activated a wider range of transcription factors than TIGR4. These data demonstrate that instead of preventing inflammatory responses the S. pneumoniae capsule causes increased pro-inflammatory responses that are relevant during infection, perhaps through restricting macrophage cell signalling responses to the bacteria. Identifying mechanisms responsible for capsule-dependent inflammation could offer opportunities for adjuvant treatment of S. pneumoniae infections.
Professor Michael Arthur UCL President and Provost Professor Michael Arthur is President and Provost of University College London. Prior to this he was Vice-Chancellor of the University of Leeds, and formerly Professor of Medicine (1992), Head of the School of Medicine (1998-2001) and Dean of the Faculty of Medicine, Health and Life Sciences in Southampton (2003-04). He is a hepatologist with research interests in liver cell biology developed initially at the University of California, San Francisco (1986-1988) and more recently as a Fulbright Distinguished Scholar at Mount Sinai School of Medicine in New York (2002). Professor Arthur became a Fellow of the Academy of Medical Sciences in
Professor Arthur has a significant national and international profile. He was Chair of the Advisory Group for National Specialised Services (NHS) (2010-2013) and was a long standing member of the Council of the Medical Research Council until recently (2006 - Sept 2014). He has also been a US/UK Fulbright Commissioner and is a former Chair of both the Worldwide Universities Network and the Russell Group of Universities. Professor Arthur took up his current post on 1 September 2013. Professor Sir John Tooke UCL Vice-Provost (Health) and Head of the UCL School of Life and Medical Sciences and the UCL Medical School Professor Sir John Tooke is Vice Provost (Health) and Head of the School of Life and Medical Sciences at UCL; Academic Director of UCL’s Academic Health Science Centre, UCLPartners; and Co-Chair of the Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation (CASMI). Sir John is President of the Academy of Medical Sciences and a past Chair of both the Medical Schools Council and the UK Healthcare Education Advisory Committee (UKHEAC). He is a member of the National Institute for Health Research (NIHR) Advisory Board and the Council for Science and Technology. His clinical and research interests focus on diabetes and its vascular complications. In 2007 he led the Inquiry for the Secretary of State for Health into Postgraduate Medical Education and Training, culminating in the final report, Aspiring to Excellence. In the same year he led a high-level group for the CMO on Barriers to Clinical Effectiveness, the report of which led to the creation of CLAHRCs (Collaborations for Leadership in Applied Health Research and Care).
Arguing ‘ Against ’: Professor John Martin Professor of Cardiovascular Medicine, Metabolism & Experimental Therapeutics, UCL Division of Medicine Adjunct Professor of Internal Medicine (Cardiology) Yale Professor John Martin first studied philosophy in Spain, followed by medicine at the University of Sheffield, training as a clinician scientist. He then worked at the University of Melbourne, Australia, and subsequently became British Heart Foundation Professor at King’s College London. At this time he was also head of cardiovascular research at the Wellcome Foundation Research Laboratories. He is now professor of cardiovascular medicine at UCL and adjunct professor of medicine at Yale University in the United States. He also held the Queen Victoria Eugenia Chair at the Complutense University in Madrid from 2004 to 2005. In 1997 he founded Ark Therapeutics Ltd, which is a biotechnology company listed on the London Stock Exchange. His research interests include platelet physiology and pathophysiology and gene therapy, particularly adenoviral expression of VEGF in the cardiovascular system. He also leads phase III clinical trials on the use of autologous bone marrow stem cells for the treatment of acute myocardial infarction. He is a Fellow of the Academy of Medicine Sciences, a Fellow of the Royal College of Physicians, a Bachelor of Surgery and Doctor of Medicine and an Honorary Doctor of Medicine in the University of Eastern Finland. He leads the Yale UCL Collaborative (with Dr Mike Simons from Yale) and is president of the European Critical Care Foundation. He is past Vice President of the European Society of Cardiology. How the debate session will work Each member of the audience will be given a voting handset when they re-enter the Lecture Theatre, after the lunch break. At the start of the debate, the audience will be asked to use their handsets to vote whether they ‘agree’ or ‘disagree’ with the proposition: ‘ All children should have genome sequencing at birth’. The results collected by the handsets will show on a graph on the screen in the Lecture Theatre. The debate will then commence, with each participant taking it in turn to set out their argument, uninterrupted. The opponents will then challenge the opposition. There will then be a chance for questions/comments from the audience. The Chair will summarise the points raised, and ask the audience to vote again, using their handsets. The audience and debaters will then be able to see if there has been any change of view as a result of the debate. The audience are asked to kindly return the voting handsets to the events stewards during the next break.
Chair: Dr Mahdad Noursadeghi Senior Lecturer UCL Division of Infection & Immunity Dr Noursadeghi studied Medicine at Guys Hospital and then undertook specialist training in Infectious Diseases with an MRC Research Training Fellowship and PhD in Immunology at Imperial College London, and a Wellcome Trust Intermediate Fellowship at UCL. Dr Noursadeghi’s research focuses on the role of macrophages in innate immune host-pathogen interactions and the application of genome-wide transcriptional profiling to study in vivo human immune responses to infection. Dr Noursadeghi is also an Honorary Consultant in Infectious Diseases and Acute Medicine at UCLH. Professor Judith Breuer Professor of Virology UCL Division of Infection & Immunity Deputy Director, MRC-UCL Centre for Medical Molecular Virology Honorary Consultant Virologist Great Ormond Street Hospital Head of UCL VZV Reference Laboratory Sex and drugs and CMV Professor Breuer's research at the MCR- UCL Centre for Molecular Virology has resulted in the successful development of methodoligies to recover low copy viral DNA from clinical samples and subsequent generation of a template suitable for whole genome sequencing, including the detection of rare variants. She is currently applying these methods to investigate the genetic association of Varicella zoster (VZV) and Herpes Simplex Virus (HSV) with different disease states. More recently Professor Breuer has developed whole genome sequencing directly from clinical material of other pathogens including Mycobacterium tuberculosis, chlamydia trachomatis, cytomegalovirus and norovirus. The data generated is providing insights into the evolution and spread of these pathogens. Other research interests include pathogenesis of alphaherpesvirus infections in the skin, and the development of novel molecular tools including a pathogen discovery pipelines to aid in diagnosis and management of infection. Professor Breuer also holds positions as Consultant Virologist at Great Ormond Street Hospital, and Head of the VZV Reference Laborator.
Chair: Professor David Abraham Professor of Cell and Molecular Biology Head of Research Department of Inflammation Director of Centre for Rheumatology and Connective Tissue Diseases UCL Division of Medicine KTE Champion, UCL Faculty of Medical Sciences David Abraham is a Professor of Cell and Molecular Biology and Head of the UCL Research Department of Inflammation where he is involved in defining research strategy. After gaining a PhD at King’s College, he held a fellowship at the Kennedy Institute for Rheumatology in London, and a Medical Research Council Travelling Fellow at Berkeley and the Jackson Laboratory in the USA. He became a senior scientist in genetics and mammalian development at the Medical Research Council's National Institute for Medical Research and then moved to UCL Division of Medicine in 1997. Professor Abraham’s major research interests include studying tissue repair processes, the pathobiology of scleroderma and the mechanisms underlying tissue scarring and fibrosis and the development and use of genetically modified mice as pre-clinical models to study fibrosis pathogenesis and treatment of connective tissue diseases. Collaborations with industrial partners have led to the successful licensing and translation of targets into clinical trials. Professor Derek W Gilroy Wellcome Trust Senior Research Fellow Head of Centre for Clinical Pharmacology UCL Division of Medicine Understanding the cellular basis of resolving inflammation in rodents and humans In 1997 Derek Gilroy obtained his PhD from The William Harvey Research Institute, Queen Mary University of London (QMUL) for investigations in the role of inducible cyclooxygenase in inflammation, working with the late Professors Derek Willoughby and Sir John Vane. Thereafter, he left The William Harvey to receive postdoctoral training with Dr Kenneth Wu, jointly at the University of Houston Texas and at Academia Sinica, Taipei, Tawian from 1998-2000. He then returned to the William Harvey Research Institute for a further four years. In 2004, Derek was appointed as New Blood lecturer funded as a Wellcome Trust Career Development Fellow at the Division of Medicine, Rayne Building, University College London. In 2009 he became a Wellcome Trust Senior Research Fellow and in 2010 was promoted to Professor of Experimental Immunology. At UCL he is now Head of the Centre for Clinical Pharmacology where he has pioneered research examining the molecular and biochemical pathways that regulates the resolution of acute immune reactions. Professor Gilroy has won the Bayer International Young Investigator Award for Aspirin Research, 2005 and the British Pharmacological Society, Norvartis Award, 2007.
Professor Kenneth Smith Professor and Head of Department of Neuroinflammation UCL Institute of Neurology Experimental evidence regarding why, how and where lesions can form in multiple sclerosis Professor Smith received a BSc in Physiology from the University of London, and then did his PhD at the UCL Institute of Neurology with Ian McDonald on the conduction properties of remyelinated axons. After a postdoctoral training at the Institute, with Hugh Bostock looking at conduction along demyelinated axons, he spent five years in Chicago examining the biophysical properties of the node of Ranvier. After a further five years in regeneration research at Virginia Professor Smith returned to the UK to take up a position on the Guy’s Hospital Campus, working with Richard Hughes where he developed an interest in neuroinflammation. The institution merged with King’s College London, and he was appointed as Professor of Neurophysiology. In 2007 he returned to the UCL Institute of Neurology and is now the Head of the Department of Neuroinflammation, where his research continues into the pathophysiological properties of the inflamed nervous system. Professor Lucy Wedderburn Professor of Paediatric Rheumatology Infection, Immunity, Inflammation and Physiological Medicine UCL Institute of Child Health Th17 and CD161: the Jekyll and Hyde of childhood arthritis? Lucy Wedderburn’s lab group has a major focus upon human T cell responses and immune regulation, in particular the autoimmune conditions of childhood, including Juvenile Idiopathic Arthritis (JIA) and Juvenile Dermatomyositis (JDM). They are interested in the mechanisms which allow survival and expansion of inflammatory T cells within the joint, the control of their production of cytokines and chemokines, and their contribution to disease. In tandem they study immune regulation and how this influences disease course and phenotype in JIA. Childhood arthritis has proved an excellent model in which to study the balance between activation and regulation in the immune system. The Wedderburn lab has shown that highly proinflammatory cells, Th17 cells, are more abundant in patients with mild forms of arthritis than those with the more severe disease type, and that Treg and Th17 cells exist in a reciprocal relationship in the joint. They have generated evidence for 'plasticity' of Th cells at the inflamed site: when Th17 convert to Th1 cells they retain the Th17 like marker, CD161. They have now identified a novel set of T regulatory cells, defined by expression of CD161 that are also pro inflammatory.
