A B Kay

Imperial College London, Londinium, England, United Kingdom

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Publications (498)4093.21 Total impact

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    A.B. Kay · P Clark · M Maurer · S Ying
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    ABSTRACT: The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of Th2 (IL-4 and IL-5) cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines (IL-33, IL-25 and TSLP), released through innate immune mechanisms, may play a role in pathogenesis. The aim was to identify Th2-initiating cytokines in lesional and non-lesional skin from CSU patients and to compare results with a control group. Paired biopsies (one from a 4- 8 hour spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU, and nine control subjects, and studied by immunohistochemistry and confocal microscopy. There were increases in IL-4(+) and IL-5(+) cells in lesional skin compared to controls (p=0.03 and p=0.0006, respectively) and marked elevations in the numbers of IL-33(+) , IL-25 (+) and TSLP(+) cells in the dermis of lesional, compared to both non-lesional skin (p=0.002, p=0.01 and p=0.04, respectively) and controls (p=0.001, p=0.0009 and p=0.005, respectively). There was also a correlation between the numbers of IL-33(+) and IL-25(+) cells (r = 0.808, p = 0.015). IL-33 localised to CD31(+) endothelial cells, CD90(+) fibroblasts, CD68(+) macrophages and tryptase(+) mast cells whereas IL-25 was expressed by epithelial cells, mast cells and MBP(+) eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and CSU. Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways may play a role in the mechanism of wealing. Since Th2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these finding may also have therapeutic implications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Dec 2014 · British Journal of Dermatology
  • A. Barry Kay
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    ABSTRACT: In 1879 Paul Ehrlich published his technique for staining blood films and his method for differential blood cell counting using coal tar dyes and mentions the eosinophil for the first time. Eosin is a bright red synthetic dye produced by the action of bromine on fluorescein and stains basic proteins due to its acidic nature. It was discovered in 1874 by Heinrich Caro, Director of the German chemical company Badische Anilin- und Soda-Fabrik. Ehrlich introduced the term “eosinophil” to describe cells with granules (which he called alpha-granules) having an affinity for eosin and other acid dyes. He also observed black-staining, indulinophilic, beta-granules in bone marrow-derived eosinophils which were probably immature crystalloid granules in eosinophil myelocytes. Ehrlich described the features of the alpha-granule and the cell's distribution in various species and tissues. He speculated correctly that the alpha-granule contents were secretory products and described several causes of eosinophilia including asthma, various skin diseases, helminths and reactions to medications. However, the cell was almost certainly observed by others before Ehrlich.. In 1846 Thomas Wharton Jones (1808-1891) described “granule blood-cells” in the lamprey, frog, fowl, horse, elephant and man. He “borrowed” the term granule cell from Julius Vogel (1814-1880) who had observed similar cells in inflammatory exudates. Vogel in turn was aware of the work of the Gottlieb (Théophile) Gluge (1812-1898) who used the term “compound inflammatory globules” to describe cells in pus and serum. Almost 20 years before Ehrlich developed his staining methods, Max Johann Sigismund Schultze (1825 -1874) performed functional experiments on coarse granular cells using a warm stage microscopic technique and showed they had amoeboid movement and phagocytic abilities. Although these early investigators recognised distinct granular cells Ehrlich's use of stains was a landmark contribution which heralded modern studies on eosinophils and other blood leucocytes.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Clinical & Experimental Allergy
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    ABSTRACT: Background The mechanisms for producing weals in chronic spontaneous (idiopathic) urticaria (CSU) are incompletely understood. Leucocyte infiltration with vascular leakage and expression of the potent vasoactive agents' calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) are features of late-phase allergic skin reactions, previously proposed as a model of CSU. Objective To measure CGRP and VEGF expression in lesional and non-lesional skin from CSU patients and to compare results with a control group. Methods Eight paired biopsies (one from 4-8 h spontaneous weals and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects and studied by immunohistochemistry and confocal microscopy. Results Lesional skin in CSU contained significantly more CGRP+ and VEGF+ cells than non-lesional skin. No significant differences were observed in CGRP and VEGF expression between non-lesional skin and controls. In lesional skin, VEGF and CGRP co-localised to UEA-1+ blood vessels. CGRP was also expressed by neutrophils and eosinophils and to a lesser extent by CD90(+) fibroblasts, mast cells, CD3(+) and CD68(+) cells. CGRP and VEGF expression was not related to the duration of disease. Conclusion and Clinical Relevance Increased expression of CGRP and VEGF in lesional, but not uninvolved, skin indicates that these potent vasoactive agents may play a role in wealing and tissue oedema in CSU so representing novel targets in therapy.
    Full-text · Article · Aug 2014 · Clinical & Experimental Allergy
  • A Barry Kay
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    ABSTRACT: There were remarkable achievements in the 19th century in our understanding of the cells of the allergic response, the clear descriptions of hay fever and asthma, as well as the role of pollen in seasonal rhinitis. Although allergy as a concept was not developed until well into the 20th century, the foundations of our present understanding of these diseases were laid in the 1800s. The outstanding physicians and scientists of this time included Paul Ehrlich (who described mast cells, eosinophils and basophils), John Bostock (who provided the first detailed account of hay fever), Charles Blackley (who showed that pollen was the cause of hay fever), Morrill Wyman (who demonstrated that autumnal catarrh was due to ragweed pollen), Henry Hide Salter (who made the first classic description of asthma) and Henri Laënnec (the inventor of the stethoscope). © 2014 S. Karger AG, Basel.
    No preview · Article · May 2014 · Chemical immunology and allergy
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    A Barry Kay · S Ying · E Ardelean · A Mlynek · H Kita · P Clark · M Maurer
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    ABSTRACT: In chronic spontaneous urticaria (CSU) mast cell activation together with inflammatory changes in the skin are well documented and may play an important role in mechanisms of tissue oedema OBJECTIVE: To confirm and extend these observations by measuring microvascular markers, leukocytes and mast cells numbers in lesional and uninvolved skin and to compare findings with a control group. Paired biopsies (one from 4- 8 hour spontaneous weals and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects and studied by immunohistochemistry and confocal microscopy using the lectin UEA-1. Lesional skin in CSU contained significantly more CD31+ endothelial cells and CD31+ blood vessels, neutrophils, eosinophils, basophils, macrophages and CD3+ T cells, than non-lesional skin. Increased vascularity was confirmed by confocal imaging using the lectin UEA-1. Uninvolved skin from CSU contained significantly more CD31+ endothelial cells, CD31+ blood vessels and eosinophils compared to the control subjects. There was a three-fold increase in mast cell numbers when CSU was compared to controls but no difference was observed between lesional and uninvolved skin. Increased vascular markers together with eosinophil and neutrophil infiltration are features of lesional skin in CSU and might contribute to tissue oedema. Eosinophils and microvascular changes persist in uninvolved skin which, together with increased mast cells, suggests that non-lesional skin is primed for further wealing. This article is protected by copyright. All rights reserved.
    Full-text · Article · Mar 2014 · British Journal of Dermatology

  • No preview · Chapter · Dec 2013
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    ABSTRACT: BACKGROUND: Calcitonin gene-related peptide (CGRP) is a potent arterial and venous vasodilator. Increased airway epithelial cell expression of CGRP, together with increased CCL17 expression, was previously observed in a model of provoked asthma in atopic human subjects. OBJECTIVE: We sought to determine whether CCL17 induces CCR4-dependent CGRP synthesis and secretion by human airway epithelial cells. METHODS: Human airway epithelial cell lines (BEAS-2B and A549) and human primary airway cells were cultured with CCL17 or various other cytokines, and CGRP expression was measured by using RT-PCR, quantitative immunofluorescence, and enzyme immunoassay. CCR4 expression was determined in cultured cells by using flow cytometry and in bronchial biopsy specimens by using immunohistochemistry. RESULTS: CCL17 induced a several thousand-fold increase in CGRP mRNA expression and released peptide product from BEAS-2B and A549 cells in a time- and concentration-dependent fashion. Concentration-dependent CCL17-induced release of CGRP by primary human airway epithelial cells was also observed. Under comparable conditions, CCL17 induced greater CGRP release from BEAS-2B cells than either IL-13, a cytokine mixture (TNF-α, GM-CSF, and IL-1), or CCL22. CCR4 was expressed by BEAS-2B and A549 cells and internalized after ligation with CCL17. CCL17-induced CGRP release was inhibited by a specific anti-CCR4 blocking antibody. Bronchial biopsy specimens obtained from healthy volunteers and asthmatic patients before and after provoked asthma all exhibited CCR4 staining of equivalent intensity, indicating that the receptor is constitutively expressed. CONCLUSIONS: CCL17-induced, CCR4-dependent release of CGRP by human airway epithelial cells represents a novel inflammatory pathway and a possible target in patients with asthma and allergic disease.
    No preview · Article · May 2013 · The Journal of allergy and clinical immunology
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    S Dreborg · T.H. Lee · A.B. Kay · S.R. Durham
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    ABSTRACT: One hundred years ago, Noon [Lancet 1911;1:1572-1573], using conjunctival provocation testing (CPT), was the first to demonstrate the effectiveness of subcutaneous immunotherapy (SCIT) in grass-allergic subjects with hay fever. In this centenary year, we present data that, by use of CPT and allergen-specific IgG, replicate this observation and additionally confirm the allergen specificity of SCIT by using a double-blind design employing either grass or mite SCIT in dual grass- and mite-allergic individuals. Twenty adults (11 females) with perennial rhinoconjunctivitis and exacerbation of symptoms during the grass pollen season and in the autumn had immediate skin and conjunctival sensitivity and raised specific IgE to both Dermatophagoides farinae and Phleum pratense. Participants were randomly assigned to either timothy or D. farinae immunotherapy for 3 years. CPT and specific IgG tests to both allergens were performed annually. After 3 years, subjects gave their blinded overall evaluation. Six mild-to-moderate general reactions occurred in 2 timothy- and 4 mite-treated patients. Four of these patients and 2 other patients withdrew from the study. Seven patients in each group completed the study. After 3 years of immunotherapy, the timothy CPT threshold concentration had increased 16- fold in timothy-treated patients (p < 0.05; between-group change, p < 0.05). The increase in the mite CPT threshold in mite- compared to grass-treated patients was 31-fold (p < 0.05). The overall assessment of conjunctival sensitivity was highly significant in favour of treatment (p < 0.015), as was that of allergen-specific IgG (p < 0.0001). Allergen immunotherapy is allergen species-specific, as judged by decreased conjunctival sensitivity and changes in allergen-specific IgG concentrations.
    Full-text · Article · Dec 2011 · International Archives of Allergy and Immunology
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    ABSTRACT: IL-25 is thought to participate in allergic inflammation by propagating T(h)2-type responses. To address the hypothesis that allergen provocation increases expression of IL-25 and its receptor IL-25R in the asthmatic bronchial mucosa and skin dermis of atopic subjects. Sequential single and double immunostaining was used to evaluate the numbers and phenotypes of IL-25 and IL-25R immunoreactive cells in bronchial biopsies from mild atopic subjects with asthma (n = 10) before and 24 hours after allergen inhalation challenge and skin biopsies from atopic subjects (n = 10) up to 72 hours after allergen subepidermal injection. IL-25 immunoreactivity was expressed by a majority of epidermal cells in both organs at baseline and was not further augmented by challenge. IL-25R immunoreactive cells were rare in the epidermis before or after challenge. Allergen challenge was associated with significantly (P < .01) increased expression of IL-25 and IL-25R immunoreactivity in the submucosa of both organs. IL-25 immunoreactivity colocalized with eosinophils, mast cells, and endothelial cells, whereas IL-25R immunoreactivity colocalized with eosinophils, mast cells, endothelial cells, and T lymphocytes. In both organs, correlations were observed between increases in IL-25 expression and the magnitudes of the late-phase allergen-induced clinical responses. Allergen provocation induces functionally relevant, increased expression of IL-25 and its receptor in the asthmatic bronchial mucosa and dermis of sensitized atopic subjects. In addition to T cells, eosinophils, mast cells, and endothelial cells are potential sources and targets of IL-25 in the course of allergic inflammation.
    No preview · Article · May 2011 · The Journal of allergy and clinical immunology
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    S. Dreborg · T. Lee · A. B. Kay · S.R. Durham

    Full-text · Article · Feb 2011 · Journal of Allergy and Clinical Immunology
  • A. B. Kay · K. Bonner · P. Clark

    No preview · Article · Feb 2011 · Journal of Allergy and Clinical Immunology
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    ABSTRACT: Allergic sensitization to cat allergens is common and represents a major risk factor for asthma. Specific immunotherapy (SIT) is effective but cumbersome and associated with IgE-dependent adverse events. Immunotherapy targeting allergen-specific T cells, with synthetic peptides representing T-cell epitopes, might improve safety and reduce the duration of treatment. We sought to define major T-cell epitopes of Fel d 1 for peptide immunotherapy, generate a peptide vaccine, and evaluate its safety and tolerability in subjects with cat allergy. We determined the binding affinities of Fel d 1 peptides for 10 commonly expressed HLA-DR molecules. Functionally immunodominant peptides were identified by means of proliferation and cytokine secretion. Histamine-releasing activity was assessed, and a peptide vaccine was formulated. Safety and tolerability were evaluated in a dose-ranging phase IIa clinical trial. MHC-binding sequences were identified throughout Fel d 1. Some regions contained multiple overlapping T-cell epitopes that bound multiple MHC molecules. Immunodominant sequences were identified on the basis of proliferative and cytokine (IFN-γ, IL-10, and IL-13) responses. Cat allergen extract, but not peptides, induced histamine release in blood basophils. A single administration of peptide vaccine was safe and well tolerated. The dose of vaccine resulting in the greatest inhibition of the late-phase skin response to intradermal whole allergen challenge was 3 nmol. Fel d 1 contains multiple overlapping MHC-binding motifs. A peptide vaccine comprising the immunodominant regions of the allergen was safe and well tolerated when given to subjects with cat allergy as a single dose. The dose of vaccine resulting in the greatest reduction in late-phase skin response was defined for future clinical development.
    No preview · Article · Feb 2011 · The Journal of allergy and clinical immunology
  • A Barry Kay
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    ABSTRACT: Allergen-induced late-phase skin reactions are characterized by erythema and edema, but the vasoactive mediators involved remain unclear. Limited evidence from human studies suggests that calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF), potent vasodilator and permeability factors, respectively, are expressed by infiltrating inflammatory cells in certain allergic tissue reactions. We sought to determine whether tissue swelling in allergen-challenged skin sites in atopic subjects is associated with the infiltration of CGRP(+) and VEGF(+) inflammatory cells. Skin biopsy specimens were obtained from atopic subjects at various times after cutaneous allergen challenge and studied by means of single and double immunohistochemistry and in situ hybridization. CGRP-immunoreactive and CGRP mRNA-positive cell numbers were increased in biopsy specimens from sites of late-phase skin reactions compared with those at the control site (P = .03 and P = .03, respectively). Their numbers paralleled the development and resolution of the edematous late-phase skin reaction, both peaking at 6 hours after allergen challenge. The majority of CGRP-immunoreactive cells were neutrophils and CD3(+) cells, whereas eosinophils were CGRP negative. VEGF-immunopositive cell numbers were also increased in 6-hour biopsy specimens from late-phase skin reactions compared with those seen at control sites (P = .001) with a lesser but significant response (P = .008) at 24 hours. VEGF(+) cells were largely eosinophils, neutrophils, and CD68(+) macrophages. Late-phase skin reactions in atopic subjects were associated with the infiltration of inflammatory cells expressing CGRP and VEGF, suggesting that these vasoactive factors might play a role in the erythema and edema characteristic of allergic inflammation. They could also be considered targets in attempts to control allergic inflammation.
    No preview · Article · Jan 2011 · The Journal of allergy and clinical immunology
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    ABSTRACT: Epithelial cell expression of calcitonin gene-related peptide (CGRP) is a feature of provoked asthma. Receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor combine to form the CGRP1 receptor. To determine whether functional RAMP1 is expressed by airway epithelial cells and whether there are alterations in asthma. BEAS-2B and A549 cells lines were studied by RT-PCR, confocal microscopy, a quantitative immunofluorescence assay, and ELISA. Bronchial biopsies from normal subjects and subjects with asthma were examined by immunohistochemistry and in situ hybridization. Inflammatory cytokines induced CGRP release and CGRP mRNA in BEAS-2B and A549 epithelial cell lines. RAMP1 was highly expressed by resting, unstimulated BEAS-2B and A549 cells. CGRP induced internalization of RAMP1 and IL-6 production, both of which were inhibited by the CGRP antagonist, CGRP(8-37). Activation of BEAS-2B and A549 cells by inflammatory cytokines induced CGRP secretion, binding of CGRP to RAMP1, and RAMP1 internalization, which was blocked by CGRP (8-37). RAMP1 immunoreactivity and RAMP1 mRNA expression in bronchial biopsies from subjects with asthma were significantly lower than in normal subjects (P = .002 and P = .007, respectively). Inhalational challenge of atopic subjects with asthma with allergen-derived peptides produced a significant decrease in the numbers of RAMP1-positive epithelial cells in responders (P = .027) but not nonresponders. Receptor activity modifying protein 1 was expressed both by airway epithelial cells in culture and in bronchial biopsies from normal subjects and internalized after epithelial cell activation through autocrine feedback of CGRP. There is an apparent dysregulation of RAMP1 in asthmatic epithelium, suggesting continuous stimulation of pathways involving CGRP.
    Full-text · Article · Oct 2010 · The Journal of allergy and clinical immunology
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    ABSTRACT: Airway remodelling is thought to be under the control of a complex group of molecules belonging to the Transforming Growth Factor (TGF)-superfamily. The Bone Morphogenetic Proteins (BMPs) belong to this family and have been shown to regulate fibrosis in kidney and liver diseases. However, the role of BMPs in lung remodelling remains unclear. BMPs may regulate tissue remodelling in asthma by controlling TGF-β-induced profibrotic functions in lung fibroblasts. Cell cultures were exposed to TGF-β1 alone or in the presence of BMP-4 or BMP-7; control cultures were exposed to medium only. Cell proliferation was assessed by quantification of the incorporation of [3H]-thymidine. The expression of the mRNA encoding collagen type I and IV, tenascin C and fibronectin in normal human lung fibroblasts (NHLF) was determined by real-time quantitative PCR and the main results were confirmed by ELISA. Cell differentiation was determined by the analysis of the expression of α-smooth muscle actin (α-SMA) by western blot and immunohistochemistry. The effect on matrix metalloproteinase (MMP) activity was assessed by zymography. We have demonstrated TGF-β1 induced upregulation of mRNAs encoding the extracellular matrix proteins, tenascin C, fibronectin and collagen type I and IV when compared to unstimulated NHLF, and confirmed these results at the protein level. BMP-4, but not BMP-7, reduced TGF-β1-induced extracellular matrix protein production. TGF-β1 induced an increase in the activity of the pro-form of MMP-2 which was inhibited by BMP-7 but not BMP-4. Both BMP-4 and BMP-7 downregulated TGF-β1-induced MMP-13 release compared to untreated and TGF-β1-treated cells. TGF-β1 also induced a myofibroblast-like transformation which was partially inhibited by BMP-7 but not BMP-4. Our study suggests that some regulatory properties of BMP-7 may be tissue or cell type specific and unveil a potential regulatory role for BMP-4 in the regulation of lung fibroblast function.
    Full-text · Article · Jun 2010 · Respiratory research
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    ABSTRACT: Both transforming growth factor (TGF)-beta(1) and activin-A have been implicated in airway remodeling in asthma, but the modulation of their specific signaling pathways after disease activation remains undefined. To define the expression kinetics of TGF-beta(1), activin-A ligands, and follistatin (a natural activin inhibitor), their type I and type II receptors (activin-like kinase[ALK]-1, ALK-5, ALK-4, TbetaRII, and ActRIIA/RIIB) and activation of signaling (via phosphorylated (p) Smad2), in the asthmatic airway after allergen challenge. Immunohistochemistry was performed on bronchial biopsies from 15 mild atopic patients with asthma (median age, 25 years; median FEV(1)% predicted, 97%) at baseline and 24 hours after allergen inhalation. Functional effects of activin-A were evaluated by using cultured normal human bronchial epithelial (NHBE) cells. pSmad2(+) epithelial cells increased at 24 hours (P = .03), and pSmad2 was detected in submucosal cells. No modulation of activin-A, follistatin, or TGF-beta(1) expression was demonstrated. Activin receptor(+) cells increased after allergen challenge: ALK-4 in epithelium (P = .04) and submucosa (P = .04), and ActRIIA in epithelium (P = .01). The TGF-beta receptor ALK-5 expression was minimal in the submucosa at baseline and after challenge and was downregulated in the epithelium after challenge (P = .02), whereas ALK-1 and TbetaRII expression in the submucosa increased after allergen challenge (P = .03 and P = .004, respectively). ALK-1 and ALK-4 expression by T cells was increased after allergen challenge. Activin-A induced NHBE cell proliferation, was produced by NHBE cells in response to TNF-alpha, and downregulated TNF-alpha and IL-13-induced chemokine production by NHBE cells. Both TGF-beta and activin signaling pathways are activated on allergen provocation in asthma. Activin-A may contribute to resolution of inflammation.
    No preview · Article · Oct 2009 · The Journal of allergy and clinical immunology
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    ABSTRACT: Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other ("linked") epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10(+) T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti-IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans.
    Full-text · Article · Jul 2009 · Journal of Experimental Medicine

  • No preview · Conference Paper · Apr 2009
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    ABSTRACT: Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7Ralpha) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4(+) T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR(+) DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR(+) and CD11c(+) cells infiltrated relatively late (24-48 h). The majority of TSLPR(+) cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7Ralpha chains. Maturation and stimulation with TSLP or polyriboinosinic-polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7Ralpha chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells(+) CD4(+) T cells. The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation.
    Full-text · Article · Feb 2009 · Allergy
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    M Gaga · Y-E Ong · F Benyahia · M Aizen · J Barkans · AB Kay
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    ABSTRACT: Monocyte chemotactic protein (MCP-1/CCL2), the ligand for CCR2 and CCR5, and macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3), the ligand for CCR1 and CCR5, are potent chemo-attractants in vitro and produce lesions in experimental animals, which resemble immediate and delayed-type hypersensitivity (DTH) reactions. CCL3 induces mononuclear cell and granulocyte infiltration in human atopic and nonatopic skin. Whether CCL2 (MCP-1) has comparable activity in man is uncertain as is the capacity of both the chemokines to elicit immediate- and DTH-like reactions in humans. Inflammatory cells were counted by immunohistochemistry in 24 and 48-h skin biopsies from atopics and nonatopics after intradermal injection of CCL2 and CCL3. Immediate (15 min) wheals-and-flares and delayed (24 and 48 h) indurations were also recorded. Both chemokines induced immediate- (15 min) and delayed (24 and 48 h) reactions, which were associated with significant infiltrations of CD68+ macrophages, CD3+, CD4+ (but not CD8+) T cells, neutrophils, and eosinophils in biopsies from injection sites. CCL2, but not CCL3, also induced infiltration of basophils. Neither chemokine produced significant changes in the numbers of tryptase+ cutaneous mast cells. There were no differences in the pattern of skin reactivity or the numbers of infiltrating leukocytes in response to CCL2 and CCL3 between atopic and nonatopic subjects. In general, maximal infiltration of inflammatory cells was observed at the 24-h, rather than the 48-h, time point. CCL2 and CCL3 induce both immediate and delayed skin reactions in atopics and nonatopics, and evoke a similar profile of local T cell/macrophage and granulocyte recruitment which, in general, confirm previous in vitro findings and in vivo experimental animal data.
    Full-text · Article · Jul 2008 · Allergy

Publication Stats

32k Citations
4,093.21 Total Impact Points


  • 1981-2014
    • Imperial College London
      • • Section of Leukocyte Biology
      • • Section of Allergy and Clinical Immunology
      • • Faculty of Medicine
      Londinium, England, United Kingdom
  • 1991-2011
    • Uppsala University
      • Department of Women's and Children's Health
      Uppsala, Uppsala, Sweden
  • 1988-2006
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • Kanagawa Children's Medical Center
      Yokohama, Kanagawa, Japan
  • 2003
    • University of Virginia
      Charlottesville, Virginia, United States
  • 2001
    • Imperial Valley College
      IPL, California, United States
  • 2000
    • Hebrew University of Jerusalem
      • Department of Pharmacology
      Yerushalayim, Jerusalem, Israel
    • Vanderbilt University
      • Department of Medicine
      Нашвилл, Michigan, United States
  • 1989-1999
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 1997
    • McGill University
      • Meakins-Christie Laboratories
      Montréal, Quebec, Canada
  • 1982-1997
    • The British Society for Allergy & Clinical Immunology
      Londinium, England, United Kingdom
  • 1996
    • University of London
      Londinium, England, United Kingdom
  • 1985-1994
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1992
    • Royal College of Physicians
      Londinium, England, United Kingdom
  • 1990-1991
    • WWF United Kingdom
      Londinium, England, United Kingdom
    • Freie Universität Berlin
      • Department of Physics
      Berlín, Berlin, Germany
  • 1984
    • University of Santiago, Chile
      CiudadSantiago, Santiago, Chile
  • 1980
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom