A5078940172- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- Immunotherapy and Immune Responses
- Liver Disease Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- MicroRNA in disease regulation
- Hepatitis C virus research
- Liver Disease and Transplantation
- Extracellular vesicles in disease
- Liver Diseases and Immunity
- Hepatitis B Virus Studies
- Systemic Lupus Erythematosus Research
- Virus-based gene therapy research
- Liver physiology and pathology
- Diabetes and associated disorders
- Viral gastroenteritis research and epidemiology
- Immunodeficiency and Autoimmune Disorders
- Neurological Complications and Syndromes
- Circular RNAs in diseases
- Iron Metabolism and Disorders
- Hematopoietic Stem Cell Transplantation
- Organ and Tissue Transplantation Research
- Atherosclerosis and Cardiovascular Diseases
King's College Hospital
2015-2024
King's College London
2014-2024
Medical Research Council
2013-2022
Hospital Clínic de Barcelona
2007-2015
University College London
2015
University of London
2015
University of Cambridge
2015
Centro de Investigación Biomédica en Red
2010-2013
Universitat de Barcelona
2007-2013
University of California, San Francisco
2011-2013
Foxp3+ CD4+ T helper cells called regulatory (T reg) play a key role in controlling reactivity to self-antigens and onset of autoimmunity. reg either arise thymus are natural (nT or generated the periphery through induction Foxp3 inducible (iT cells. The relative contributions iT nT peripheral tolerance remain unclear as result an inability separate these two subsets Using combination novel TCR transgenic mice with defined self-antigen specificity conventional mouse models, we demonstrate...
Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred as 'operationally' tolerant. Immune characterization these patients, however, has not been performed detail, and we lack tests capable identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study have analyzed a variety biological traits peripheral blood operationally an attempt define multiparameter 'fingerprint' tolerance. Thus,...
A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and said be operationally tolerant the transplant. However, accurate identification these remains a challenge. To design clinically applicable molecular test operational tolerance in transplantation, we studied transcriptional patterns peripheral blood 80 16 nontransplanted healthy individuals by employing oligonucleotide microarrays quantitative real-time PCR....
Lifelong immunosuppression increases morbidity and mortality in liver transplantation. Discontinuation of immunosuppressive drugs could lessen this burden, but the safety, applicability, clinical outcomes strategy need to be carefully defined. We enrolled 102 stable recipients at least 3 years after transplantation a single-arm multicenter withdrawal trial. Drugs were gradually discontinued over 6 9-month period. The primary endpoint was development operational tolerance, defined as...
Regulatory T cells (Tregs) are a lymphocyte subset with intrinsic immunosuppressive properties that can be expanded in large numbers ex vivo and have been shown to prevent allograft rejection promote tolerance animal models. To investigate the safety, applicability, biological activity of autologous Treg adoptive transfer humans, we conducted an open-label, dose-escalation, Phase I clinical trial liver transplantation. Patients were enrolled while awaiting transplantation or 6-12 months...
Following organ transplantation, lifelong immunosuppressive therapy is required to prevent the host immune system from destroying allograft. This can cause severe side effects and increased recipient morbidity mortality. Complete cessation of drugs has been successfully accomplished in selected transplant recipients, providing proof principle that operational allograft tolerance attainable clinical transplantation. The intra-graft molecular pathways associated with successful drug...
// Niloufar Safinia 1,* , Trishan Vaikunthanathan Henrieta Fraser 1 Sarah Thirkell Katie Lowe Laura Blackmore 2 Gavin Whitehouse Marc Martinez-Llordella Wayel Jassem Alberto Sanchez-Fueyo Robert I. Lechler and Giovanna Lombardi MRC Centre for Transplantation, Division of Transplantation Immunology Mucosal Biology, King's College London, Guy's Hospital, UK Institute Liver Studies, * Co-first author Correspondence to: Safinia, email: Lombardi, Keywords : regulatory T cells, tolerance,...
Liver transplantation (LT) is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of losing their chance transplant attributed to decompensation (LD) and death. Ischemia/reperfusion injury (IRI) following conventional cold storage (CS) major cause leading graft loss after LT. Normothermic machine perfusion (NMP), method preservation, provides oxygen nutrition during preservation allows aerobic metabolism. NMP has recently been shown enable...
Extracellular vesicles (EVs) are responsible for a multitude of physiological functions, including immunomodulation. A heterogenous mixture small EV subsets, putative exosomes, is derived when commonly used 'exosome' isolation techniques employed. Subset diversity relates in part to their different intracellular origins, and can be associated with distinct functional properties. Recent progress the field has enabled categorization such subsets based on surface composition. For first time, we...
Significance Preservation and/or enhancement of Treg function is becoming a key component modern immunotherapeutic strategies, but the direct influence many immunosuppressive drugs on Tregs remains unknown. Calcineurin inhibitors (CNIs), which are widely used to treat inflammatory disorders, reduce size pool substantially, and this reduction might hinder their overall beneficial effects. Here we show that decrease in numbers caused by increased cell death as result limited availability IL-2...
During the initial hours after activation, CD4+ T cells experience profound changes in gene expression. Co-stimulation via CD28 receptor is required for efficient activation of naive cells. However, transcriptional consequences co-stimulation are not completely understood. We performed expression microarray analysis to elucidate effects signals on transcriptome activated show that transcription factor DEC1 highly induced a CD28-dependent manner upon cell involved essential effector...
Defective immune regulation plays a permissive role enabling effector cells to initiate and perpetuate tissue damage, eventually resulting in autoimmune disease. Numerical functional regulatory T‐cell (Treg) impairment has been previously reported liver disease (AILD; including hepatitis sclerosing cholangitis ASC). However, these early reports, Tregs were phenotypically defined as CD4 + CD25 or high cells. In the current study, we reexamined phenotypic properties of by adopting more refined...
CD4
Achieving drug-free tolerance or successfully using only small doses of immunosuppression is a major goal in organ transplantation. To investigate the potential mechanisms by which some kidney transplant recipients can achieve operational tolerance, we compared expression profiles microRNA peripheral blood mononuclear cells operationally tolerant patients with those stable treated conventional immunosuppression. B from overexpressed miR-142-3p. The miR-142-3p was over time and not modulated...
Persistent HCV infection does not preclude the establishment of liver allograft tolerance in humans.
Lim, Tiong Y.; Martinez‐Llordella, Marc; Kodela, Elisavet; Gray, Elisabeth; Heneghan, Michael A.; Sanchez‐Fueyo, Alberto , M.D., Ph.D. Author Information
Dysregulated inflammatory responses and oxidative stress are key pathogenic drivers of chronic diseases such as liver cirrhosis (LC). Regulatory T cells (Tregs) essential to prevent excessive immune activation maintain tissue homeostasis. While cues well known modulate the function stability Tregs, extent which Tregs influenced by has not been fully explored.
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...