G S Ogg

NIHR Oxford Biomedical Research, Oxford, England, United Kingdom

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Publications (168)1038.53 Total impact

  • Maryam Salimi, Graham Ogg
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    ABSTRACT: Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367-1371, 2010, Nat Rev Immunol 13: 145-149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid cell family and discuss their function in the skin and during inflammation.
    BMC Dermatology 11/2014; 14(1):18.
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    ABSTRACT: Background Early detection of complications significantly reduces dengue associated mortality and morbidity. We set out to determine if the NS1 rapid antigen detection test could be used as a point of care test to predict severe disease.Methods186 adult patients with confirmed dengue were enrolled during day 3¿8 of illness. Clinical and laboratory parameters were recorded during the course of the illness and NS1 antigen levels were determined using both the Panbio dengue early ELISA (Panbio, Australia) and a NS1 rapid antigen detection kit (SD Bioline, South Korea).Results59.1% of patients presented to hospital on day 5¿6 of illness when NS1 antigen positivity was significantly (p¿=¿0.008) associated with severe dengue (odds ratio 3.0, 95% CI 1.39 to 6.47) and the NS1 antigen levels were significantly higher (p¿=¿0.03) in those who went on to develop shock. Serum NS1 antigen levels significantly (p¿<¿0.0001) and inversely correlated with the total white cell counts and lymphocyte counts. The bedside NS1 test showed comparable sensitivity (97.4%) and specificity (93.7%) to the laboratory NS1 test in our setting and cohort.ConclusionNS1 antigen positivity is associated with a higher risk of developing severe dengue especially when positive beyond day 5 of illness in our cohort, and while further validation studies are required, the test can therefore potentially be used as a bedside point of care test as a warning sign of severe dengue.
    BMC Infectious Diseases 10/2014; 14(1):570. · 3.03 Impact Factor
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    ABSTRACT: Prostaglandin D2 (PGD2) and cysteinyl leukotrienes (cysLTs) are lipid mediators derived from mast cells, which activate TH2 cells. The combination of PGD2 and cysLTs (notably cysteinyl leukotriene E4 [LTE4]) enhances TH2 cytokine production. However, the synergistic interaction of cysLTs with PGD2 in promoting TH2 cell activation is still poorly understood. The receptors for these mediators are drug targets in the treatment of allergic diseases, and hence understanding their interaction is likely to have clinical implications. We aimed to comprehensively define the roles of PGD2, LTE4, and their combination in activating human TH2 cells and how such activation might allow the TH2 cells to engage downstream effectors, such as neutrophils, which contribute to the pathology of allergic responses. The effects of PGD2, LTE4, and their combination on human TH2 cell gene expression were defined by using a microarray, and changes in specific inflammatory pathways were confirmed by means of PCR array, quantitative RT-PCR, ELISA, Luminex, flow cytometry, and functional assays, including analysis of downstream neutrophil activation. Blockade of PGD2 and LTE4 was tested by using TM30089, an antagonist of chemoattractant receptor-homologous molecule expressed on TH2 cells, and montelukast, an antagonist of cysteinyl leukotriene receptor 1. PGD2 and LTE4 altered the transcription of a wide range of genes and induced diverse functional responses in TH2 cells, including cell adhesion, migration, and survival and cytokine production. The combination of these lipids synergistically or additively enhanced TH2 responses and, strikingly, induced marked production of diverse nonclassical TH2 inflammatory mediators, including IL-22, IL-8, and GM-CSF, at concentrations sufficient to affect neutrophil activation. PGD2 and LTE4 activate TH2 cells through different pathways but act synergistically to promote multiple downstream effector functions, including neutrophil migration and survival. Combined inhibition of both PGD2 and LTE4 pathways might provide an effective therapeutic strategy for allergic responses, particularly those involving interaction between TH2 cells and neutrophils, such as in patients with severe asthma. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
    The Journal of allergy and clinical immunology. 10/2014;
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    ABSTRACT: Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity.
    Immunity 07/2014; · 19.80 Impact Factor
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    ABSTRACT: Histamine is an abundant mediator accumulating in the skin of atopic patients where it is thought to be immune cell-derived. While keratinocytes express histidine decarboxylase (HDC), levels of the enzyme in normal or diseased epidermis and factors that influence its expression in human keratinocytes are not known.
    British Journal of Dermatology 06/2014; · 3.76 Impact Factor
  • Clinical Immunology 04/2014; · 3.77 Impact Factor
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    ABSTRACT: The role of the epidermis in the immune response is well known. While multiple cytokines are implicated in keratinocyte-mediated infection clearance and wound healing, little is known about the involvement of keratinocytes in promoting resolution of inflammation. To assess effects of histamine stimulation on keratinocyte function. We performed a combined microarray/Gene Ontology analysis of histamine-stimulated keratinocytes. Functional changes were tested by apoptosis assessment and scratch assays. Histamine receptor involvement was also assessed by blocking wound closure with specific antagonists. Histamine treatment had extensive effects on keratinocytes, including effects on proinflammatory responses and cellular functions promoting wound healing. At the functional level, there was reduced apoptosis and enhancement of wound healing in vitro. At the receptor level, we identified involvement of all keratinocyte-expressed histamine receptors (HRHs), with HRH1 blockage resulting in the most prominent effect. Histamine activates wound healing and infection clearance-related functions of keratinocytes. While enhancement of histamine-mediated wound healing is mediated predominantly via the HRH1 receptor, other keratinocyte-expressed receptors are also involved. These effects could promote resolution of skin inflammation caused by infection or superficial injury.
    Clinical and Experimental Dermatology 01/2014; · 1.33 Impact Factor
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    ABSTRACT: Vascular leak is the hallmark of severe dengue infections and leads to complications such as shock and multi-organ failure. Although many mediators have been implicated in the vascular leak in dengue, the role of sphingosine 1-phosphate (S1P) has not been investigated. As S1P has been shown to be important in barrier integrity, we assessed the S1P levels in 28 patients with acute dengue and 12 healthy individuals. The S1P levels were significantly lower in patients with acute dengue (p = 0.002) and the levels in patients with grade IV dengue haemorrhagic fever (DHF) were significantly lower than those with dengue fever (p = 0.005). We then investigated the kinetics of S1P levels throughout the course of the illness in another 32 patients in serum samples obtained twice a day. We found that S1P levels were low throughout the course of illness and S1P levels were <0.5 µM in 12/23 patients with DHF when compared to 1/9 with DF. As S1P has shown to be important in the endothelial barrier integrity and increases transendothelial resistance, low levels of S1P in acute dengue infection are likely to contribute to increased vascular permeability.
    PLoS ONE 01/2014; 9(11):e113394. · 3.53 Impact Factor
  • Clinical Immunology. 01/2014;
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    ABSTRACT: The role of epidermal barrier genes in the pathogenesis of atopic skin inflammation has recently been highlighted. Cytokines that are abundant in the skin during inflammation have been shown to exert various effects on the expression of barrier genes, although the role of histamine in this area of skin biology is not yet fully understood.
    Journal of investigational allergology & clinical immunology. 01/2014; 24(4):231-9.
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    ABSTRACT: Activation of the group 2 innate lymphoid cell (ILC2) population leads to production of the classical type 2 cytokines, thus promoting type 2 immunity. Chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2), a receptor for prostaglandin D2 (PGD2), is expressed by human ILC2s. However, the function of CRTH2 in these cells is unclear. We sought to determine the role of PGD2 and CRTH2 in human ILC2s and compare it with that of the established ILC2 activators IL-25 and IL-33. The effects of PGD2, IL-25, and IL-33 on the cell migration, cytokine production, gene regulation, and receptor expression of ILC2s were measured with chemotaxis, ELISA, Luminex, flow cytometry, quantitative RT-PCR, and QuantiGene assays. The effects of PGD2 under physiologic conditions were evaluated by using the supernatant from activated mast cells. PGD2 binding to CRTH2 induced ILC2 migration and production of type 2 cytokines and many other cytokines. ILC2 activation through CRTH2 also upregulated the expression of IL-33 and IL-25 receptor subunits (ST2 and IL-17RA). The effects of PGD2 on ILC2s could be mimicked by the supernatant from activated human mast cells and inhibited by a CRTH2 antagonist. PGD2 is an important and potent activator of ILC2s through CRTH2 mediating strong proallergic inflammatory responses. Through IgE-mediated mast cell degranulation, these innate cells can also contribute to adaptive type 2 immunity; thus CRTH2 bridges the innate and adaptive pathways in human ILC2s.
    The Journal of allergy and clinical immunology 12/2013; · 12.05 Impact Factor
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    ABSTRACT: Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.
    Journal of Experimental Medicine 12/2013; · 13.21 Impact Factor
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    ABSTRACT: Comprehensive antigenic characterization of a T cell population of unknown specificity is challenging. Existing MHC class I expression systems are limited by the practical difficulty of probing cell populations with an MHC class I peptide library and the cross-reactivity of T cells that are able to recognise many variants of an index peptide. Using emulsion PCR and emulsion in vitro transcription/translation of a random library of peptides conjugated to CD8-null HLA-A*0201 on beads, we probed HLA-A*0201-restricted T cells with specificity for influenza, CMV and EBV. We observed significant enrichment for sequences containing HLA-A2 anchors and correct viral fragments for all T cell populations. HLA bead display provides a novel approach to identify the specificity of T cells.
    Journal of immunological methods 12/2013; · 2.35 Impact Factor
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    ABSTRACT: Genotyping of wild type of varicella zoster virus (VZV) in Sri Lanka would help to distinguish the VZV wild type infection from varicella vaccine associated infections. PCR-RFLP analysis of VZV ORF 38, 54 and 62 was used for genotyping in VZV from blood or vesicular fluid from 31 patients with chickenpox or herpes zoster. The PstI restriction site of ORF 38, BglI restriction site of ORF 54 and SmaI restriction site of ORF 62 were analyzed using RFLP to determine the genotype. Except for one strain, all other VZV isolates had the genotype characteristic of the wild type VZV strain PstI+BglI+ SmaI-, which was characteristic of the Asian strain. None of the isolates had the American or the European VZV profile (PstI+BglI-) but were similar to isolates from Africa and Asia (PstI+BglI+). Interestingly, one of the VZV strains isolated from a patient with chickenpox had the characteristic genotype of the vaccine strain PstI- BglI+ SmaI+. The genotype of the VZV in Sri Lanka is similar to the Asian VZV genotype and can be easily distinguished from the VZV vaccine strain by using the polymorphisms in ORF 38, ORF 54 and ORF 62.
    Ceylon Medical Journal 12/2013; 58(4):153-6.
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    ABSTRACT: Dengue viral infections are the commonest mosquito borne viral infection in the world, affecting more than 100 countries and 390 million individuals annually. Currently, there are no effective antiviral drugs or an effective vaccine to prevent infection. A main hurdle in developing a safe and effective vaccine has been our poor understanding of the complex nature of the protective immune response in acute dengue infection and the presence of four dengue virus (DV) serotypes that are highly homologous. The role of DV specific T cells in the pathogenesis of severe clinical disease in not clear. It has been speculated that highly cross reactive T cells for the previous infecting heterologous DV serotype, which produce pro-inflammatory cytokines, contribute to disease pathogenesis. These cross reactive T cells are believed to be suboptimal in clearing the infection with the current DV-serotype. However, other studies have shown that cross-reactive DV-specific T cells are absent or present in very low frequency during acute infection, appearing only during the convalescent period in the majority of patients. Furthermore, significant apoptosis of T cells occurs in severe acute clinical disease. Overall therefore, it is unclear what role T cells play in contributing to disease pathogenesis during acute dengue infection. Existing data have been complicated by cross-reactivity in T cells assays. These findings can now be re-evaluated in the light of novel technologies to identify serotype-specific T cell responses.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 10/2013; · 3.12 Impact Factor
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    ABSTRACT: Several studies have shown that serum IL-10, IFNgamma and MIF are elevated in patients in severe dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult dengue patients with varying severity of dengue infection. Serum IL-10 levels were determined in 259 of whom 40 had severe dengue infection. Serum IFNgamma andIFNalpha levels were done in 78 and MIF levels were done in 65 patients with acute dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = -0.23, p = 0.0002) and lymphocyte counts (R = -0.29, p < 0.0001) but significantly and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01) and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did not have a good predictive value in discriminating those who were likely to develop SD (AUC = 0.66). Serum IFNgamma levels were also significantly higher (p = 0.04) in patients with SD when compared to non SD. There was no difference (p = 0.34) in serum IFNalpha levels and serum MIF levels (p = 0.15) in patients with SD and non SD. Although serum IL-10 was significantly elevated in patients with SD it had a poor discriminatory value in identifying those with SD and non SD and therefore, is unsuitable to be used as a robust biomarker in this cohort.
    BMC Infectious Diseases 07/2013; 13(1):341. · 3.03 Impact Factor
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    ABSTRACT: Studies published in recent years have highlighted the role of epidermal barrier defects in both atopic skin disease and the development of broader allergic manifestations. While genetic determinants of barrier function are important, it is clear that local acquired effects are also involved in disease pathogenesis. In this review, we aimed to summarize the known influences of cytokines abundantly expressed during atopic skin disease on components of epidermal barrier integrity and function.
    Clinical & Experimental Allergy 06/2013; 43(6):586-598. · 4.79 Impact Factor
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    ABSTRACT: We investigated the relationship between varicella zoster virus (VZV)-specific memory CD4(+) T cells and CD4(+)Foxp3(+) regulatory T cells (Tregs) that accumulate after intradermal challenge with a VZV skin test Ag. VZV-specific CD4(+) T cells were identified with a MHC class II tetramer or by intracellular staining for either IFN-γ or IL-2 after Ag rechallenge in vitro. VZV-specific T cells, mainly of a central memory (CD45RA(-)CD27(+)) phenotype, accumulate at the site of skin challenge compared with the blood of the same individuals. This resulted in part from local proliferation because >50% of tetramer defined Ag-specific CD4(+) T cells in the skin expressed the cell cycle marker Ki67. CD4(+)Foxp3(+) T cells had the characteristic phenotype of Tregs, namely CD25(hi)CD127(lo)CD39(hi) in both unchallenged and VZV challenged skin and did not secrete IFN-γ or IL-2 after antigenic restimulation. The CD4(+)Foxp3(+) T cells from unchallenged skin had suppressive activity, because their removal led to an increase in cytokine secretion after activation. After VZV Ag injection, Foxp3(+)CD25(hi)CD127(lo)CD39(hi) T cells were also found within the VZV tetramer population. Their suppressive activity could not be directly assessed by CD25 depletion because activated T cells in the skin were also CD25(+). Nevertheless, there was an inverse correlation between decreased VZV skin responses and proportion of CD4(+)Foxp3(+) T cells present, indicating indirectly their inhibitory activity in vivo. These results suggest a linkage between the expansion of Ag-specific CD4(+) T cells and CD4(+) Tregs that may provide controlled responsiveness during Ag-specific stimulation in tissues.
    The Journal of Immunology 01/2013; · 5.52 Impact Factor
  • New England Journal of Medicine 01/2013; 368(18):1695-1703. · 54.42 Impact Factor
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    ABSTRACT: Although peptides are well recognised biological molecules in vivo, their selection from libraries is challenging because of relative low affinity whilst in linear conformation. We hypothesized that multiplexed peptides and DNA on the surface of beads would provide a platform for enhanced avidity and the selection of relevant peptides from a library (ORBIT bead display). Using human immunodeficiency virus (HIV-1) gp120 as a target, we identify peptides that inhibit HIV-1 replication in vitro through blocking of protein:protein interaction with the co-receptor CCR5. The bead display approach has many potential applications for probing biological systems and for drug lead development.
    Scientific Reports 01/2013; 3:3030. · 5.08 Impact Factor

Publication Stats

11k Citations
1,038.53 Total Impact Points

Institutions

  • 2008–2014
    • NIHR Oxford Biomedical Research
      Oxford, England, United Kingdom
  • 1999–2014
    • University of Oxford
      • • MRC Human Immunology Unit
      • • Nuffield Department of Clinical Medicine
      • • Weatherall Institute of Molecular Medicine
      Oxford, England, United Kingdom
  • 1998–2014
    • Oxford University Hospitals NHS Trust
      • Nuffield Department of Medicine
      Oxford, England, United Kingdom
    • Ludwig Institute for Cancer Research
      La Jolla, California, United States
  • 2012
    • University of Sri Jayewardenepura
      Columbo, Western, Sri Lanka
  • 2002–2009
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
  • 2005
    • The Institute for Molecular Medicine
      Huntington Beach, California, United States
  • 1999–2004
    • University College London
      Londinium, England, United Kingdom
    • Imperial College London
      • Faculty of Medicine
      London, ENG, United Kingdom
  • 2001
    • J. David Gladstone Institutes
      San Francisco, California, United States
  • 2000–2001
    • The Rockefeller University
      • Laboratory of Cellular Physiology and Immunology
      New York City, New York, United States