Gary Reynolds

Gary Reynolds
Newcastle University | NCL · Institute of Cellular Medicine

BSc, MBBS

About

46
Publications
13,799
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3,194
Citations
Citations since 2016
41 Research Items
3163 Citations
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20162017201820192020202120220200400600800
20162017201820192020202120220200400600800
20162017201820192020202120220200400600800
Introduction
Skills and Expertise

Publications

Publications (46)
Presentation
Background: Patients with suspected new-onset giant cell arteritis (GCA) require urgent specialist assessment to establish a diagnosis. Early review reduces unnecessary treatment with high dose glucocorticoids in those without GCA and enhances sensitivity of temporal artery ultrasound. Ensuring patients are rapidly triaged and diagnosed poses a log...
Article
Full-text available
It is not fully understood why COVID-19 is typically milder in children1–3. To examine differences in response to SARS-CoV-2 infection in children and adults, we analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy...
Article
Full-text available
The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we apply single-c...
Conference Paper
Full-text available
Introduction and Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Whilst a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. However, the underlying mecha...
Preprint
Full-text available
Common genetic variants modulate the cellular response to viruses and are implicated in a range of immune pathologies, including infectious and autoimmune diseases. The transcriptional antiviral response is known to vary between infected cells from a single individual, yet how genetic variants across individuals modulate the antiviral response (and...
Article
Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transc...
Preprint
Full-text available
Throughout postnatal life, haematopoiesis in the bone marrow (BM) maintains blood and immune cell production. Haematopoiesis first emerges in human BM at 12 post conception weeks while fetal liver (FL) haematopoiesis is still expanding. Yet, almost nothing is known about how fetal BM evolves to meet the highly specialised needs of the fetus and new...
Article
Full-text available
Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood...
Article
Full-text available
Purpose Single cell (sc) analyses of key embryonic, fetal and adult stages were performed to generate a comprehensive single cell atlas of all the corneal and adjacent conjunctival cell types from development to adulthood. Methods Four human adult and seventeen embryonic and fetal corneas from 10 to 21 post conception week (PCW) specimens were dis...
Preprint
Full-text available
While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infecti...
Preprint
Full-text available
The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we applied single-cell...
Article
Full-text available
Cellular beauty is skin deep Human skin works as barrier, preventing the entry of pathogens, among other functions. Reynolds et al. used single-cell sequencing to generate an atlas of the human skin from both developing and adult sources, identifying differences and similarities across heterogeneous populations of skin cells. In this atlas, gene ex...
Preprint
Full-text available
The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 periphera...
Preprint
Full-text available
The human skin confers biophysical and immunological protection through a complex cellular network that is established early in development. We profiled ~500,000 single cells using RNA-sequencing from healthy adult and developing skin, and skin from patients with atopic dermatitis and psoriasis. Our findings reveal a predominance of innate lymphoid...
Preprint
To study the development and composition of human ocular surface, we performed single cell (sc) RNA-Seq at key embryonic, fetal and adult stages and generated the first atlas of the corneal cell types from development to adulthood. Our data indicate that during development, the conjunctival epithelium is the first to be specified from the ocular su...
Article
Full-text available
Myelopoiesis is invariably present, and contributes to pathology, in animal models of graft versus host disease (GVHD). In humans, a rich inflammatory infiltrate bearing macrophage markers has also been described in histological studies. In order to determine the origin, functional properties and role in pathogenesis of these cells, we isolated sin...
Article
Background Tocilizumab was approved for the treatment of giant cell arteritis (GCA) by NICE in April 2018. This decision followed the GiACTA (Giant Cell Arteritis Actemra) study, a randomised control trial that demonstrated a beneficial effect of tocilizumab in reducing the frequency of disease flare and overall prednisolone requirements. However,...
Article
Background Giant cell arteritis (GCA) is the commonest large-vessel vasculitis. Until recently high dose corticosteroids had been the mainstay of treatment. Significant concern about steroid related co-morbidities have driven interest in developing new treatment strategies, and the potential to reduce costs associated with managing these complicati...
Article
Background False positive and negative GCA diagnoses lead to significant morbidity. GCA Fast Track Pathways (GCA-FTP) are advocated in the NHS. Concern that these become ‘headache clinics’, lack of access to temporal artery ultrasound (TAUS) and biopsy (TAB) are cited as barriers to provision. We present prospectively collected data from referrals...
Article
Thymus development, cell by cell The human thymus is the organ responsible for the maturation of many types of T cells, which are immune cells that protect us from infection. However, it is not well known how these cells develop with a full immune complement that contains the necessary variation to protect us from a variety of pathogens. By perform...
Preprint
Full-text available
The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We utilised single-cell RNA-sequencing (scRNA-seq) to create a cell census of the human thymus and to reconstruct T-cell differentiation trajectories and T-cell receptor (TCR) rec...
Article
Full-text available
Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) and are traditionally defined as being BDCA-2+CD123+. pDCs are not readily detectable in healthy human skin, but have been suggested to accumulate in wounds. Here, we describe a CD1a-bearing BDCA-2+CD123int DC subset that rapidly infiltrates human skin wounds and comprises a majo...
Article
Full-text available
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of huma...
Preprint
Full-text available
Myelopoiesis is invariably present, and contributes to pathology, in animal models of graft versus host disease (GVHD). In humans, a rich inflammatory infiltrate bearing macrophage markers has also been described in histological studies. In order to determine the origin, functional properties and role in pathogenesis of these cells, we isolated sin...
Preprint
Full-text available
Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs), yet remains poorly defined in humans. Using single cell transcriptome profiling of ~133,000 fetal liver and ~65,000 fetal skin and kidney cells, we identify the repertoire of blood and immune cells...
Article
Full-text available
Mononuclear phagocytes (MPs) including monocytes, macrophages and dendritic cells (DCs) are critical innate immune effectors and initiators of the adaptive immune response. MPs are present in the alveolar airspace at steady state, however little is known about DC recruitment in acute pulmonary inflammation. Here we use lipopolysaccharide inhalation...
Article
Full-text available
Osteoarthritis (OA) is a leading cause of disability, globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target inflammation therapeutically have had limited success. A better understanding of the cellular and molecular processes occurring in the OA synovium is needed to develop novel therapeutics. We inves...
Article
Objective The study aims to assess targeted simulation courses, including live animal operating as complimentary training tools with regard to two key surgical skills in early cardiothoracic training. Methods Twenty UK surgical trainees (equivalent to cardiothoracic residents in the USA) in their first year of residency training were evaluated. As...
Article
What's in a drop of blood? Blood contains many types of cells, including many immune system components. Immune cells used to be characterized by marker-based assays, but now classification relies on the genes that cells express. Villani et al. used deep sequencing at the single-cell level and unbiased clustering to define six dendritic cell and fou...
Article
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T-cells. Lack of IL-12p70 pro...
Article
Background Dendritic cells specialise in initiating adaptive immune responses. The CD1c+ subset in human beings is proposed to excel at CD4+ T cell priming. An equivalent population in mice has been shown to be heterogeneous and contain functionally distinct monocyte-related and conventional dendritic cell-related subpopulations. We aimed to examin...
Article
Full-text available
Dendritic cells (DCs), monocytes, and macrophages are a heterogeneous population of mononuclear phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumor, and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as...
Article
Full-text available
A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. Production of GM-CSF by peripheral bloo...
Article
The capacity of dendritic cells (DC) to regulate adaptive immunity is controlled by their maturation state and lifespan. Although TNF is a well-known maturation and survival factor for DC, the role of the two TNFR, TNFR1 and TNFR2, in mediating these effects is poorly understood. By using unique TNF variants that selectively signal through TNFR1 an...
Article
Full-text available
Novel treatments in development for rheumatoid arthritis target three broad areas: cytokines, cells and signaling pathways. Therapies from each domain share common advantages (for example previously demonstrated efficacy, potential long-term immunomodulation and oral administration respectively) that have stimulated research in each area but also c...
Article
Biologic therapies have been licensed to treat rheumatic diseases for more than a decade. In parallel, they have gained acceptance in a variety of non-rheumatic diseases, where their impact has been no less revolutionary. In this Review, we examine the application of biologics in a number of non-rheumatic autoimmune and inflammatory disorders-psori...

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