Publications
51 results found
Cook J, Martin-Alonso A, Sanghani N, et al., 2018, Children with Pre-School Wheeze Have Neutrophilic Airway Inflammation Associated with Bacteria and Viruses During Periods of Clinical Stability, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Byrne AJ, Weiss M, Mathie SA, et al., 2016, A critical role for IRF5 in regulating allergic airway inflammation, Mucosal Immunology, Vol: 10, Pages: 716-726, ISSN: 1935-3456
Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of theexpression of pro-inflammatory cytokine and responses to infection, however its role in regulatingpulmonary immune responses to allergen is unknown. We used genetic ablation, adenoviralvector-driven overexpression and adoptive transfer approaches to interrogate the role of IRF5 inpulmonary immunity and during challenge with the aero-allergen, house dust mite. Global IRF5deficiency resulted in impaired lung function and extracellular matrix (ECM) deposition. IRF5was also essential for effective responses to inhaled allergen, controlling airway hyper-responsiveness, mucus secretion and eosinophilic inflammation. Adoptive transfer of IRF5-deficient alveolar macrophages into the WT pulmonary milieu was sufficient to drive airwayhyper-reactivity, at baseline or following antigen challenge. These data identify IRF5-expressingmacrophages as a key component of the immune defence of the airways. Manipulation of IRF5activity in the lung could therefore be a viable strategy for the redirection of pulmonary immuneresponses and thus, the treatment of lung disorders.
Byrne AJ, Maher TM, Lloyd CM, 2016, Pulmonary macrophages: a new therapeutic pathway in fibrosing lung disease?, Trends in Molecular Medicine, Vol: 22, Pages: 303-316, ISSN: 1471-4914
Pulmonary fibrosis (PF) is a growing clinical problem which can result in breathlessness or respiratory failure and has an average life expectancy of 3 years from diagnosis. Therapeutic options for PF are limited and there is therefore a significant unmet clinical need. The recent resurgent interest in macrophage biology has led to a new understanding of lung macrophage origins, biology, and phenotypes. In this review we discuss fibrotic mechanisms and focus on the role of macrophages during fibrotic lung disease. Data from both human and murine studies are reviewed, highlighting novel macrophage-orientated biomarkers for disease diagnosis and potential targets for future anti-fibrotic therapies.
Allden SJ, Toshner RJ, Byrne AJ, et al., 2016, Expression Of Cd71 On Alveolar Macrophages Reveals Distinct Cell Populations In Human Bronchoalveolar Lavage From Patients With Interstitial Lung Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Toshner RJ, Allden SJ, Byrne AJ, et al., 2016, The Il-33/st2 Axis Is Upregulated In Fibrotic Lung Disease, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Byrne AJ, Mathie SA, Gregory LG, et al., 2015, Pulmonary macrophages: key players in the innate defence of the airways, THORAX, Vol: 70, Pages: 1189-1196, ISSN: 0040-6376
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- Citations: 285
Denney L, Byrne A, Shea T, et al., 2015, Pulmonary epithelial cell-derived cytokine TGF-β1 Is a critical cofactor for enhanced innate lymphoid cell function, Immunity, Vol: 43, Pages: 945-958, ISSN: 1097-4180
Epithelial cells orchestrate pulmonary homeostasis and pathogen defense and play a crucial role in the initiation of allergic immune responses. Maintaining the balance between homeostasis and inappropriate immune activation and associated pathology is particularly complex at mucosal sites that are exposed to billions of potentially antigenic particles daily. We demonstrated that epithelial cell-derived cytokine TGF-β had a central role in the generation of the pulmonary immune response. Mice that specifically lacked epithelial cell-derived TGF-β1 displayed a reduction in type 2 innate lymphoid cells (ILCs), resulting in suppression of interleukin-13 and hallmark features of the allergic response including airway hyperreactivity. ILCs in the airway lumen were primed to respond to TGF-β by expressing the receptor TGF-βRII and ILC chemoactivity was enhanced by TGF-β. These data demonstrate that resident epithelial cells instruct immune cells, highlighting the central role of the local environmental niche in defining the nature and magnitude of immune reactions.
Weiss M, Byrne AJ, Blazek K, et al., 2015, IRF5 controls both acute and chronic inflammation, Proceedings of the National Academy of Sciences of the United States of America, Vol: 112, Pages: 11001-11006, ISSN: 0027-8424
Whereas the importance of macrophages in chronic inflammatory diseases is well recognized, there is an increasing awareness that neutrophils may also play an important role. In addition to the well-documented heterogeneity of macrophage phenotypes and functions, neutrophils also show remarkable phenotypic diversity among tissues. Understanding the molecular pathways that control this heterogeneity should provide abundant scope for the generation of more specific and effective therapeutics. We have shown that the transcription factor IFN regulatory factor 5 (IRF5) polarizes macrophages toward an inflammatory phenotype. IRF5 is also expressed in other myeloid cells, including neutrophils, where it was linked to neutrophil function. In this study we explored the role of IRF5 in models of acute inflammation, including antigen-induced inflammatory arthritis and lung injury, both involving an extensive influx of neutrophils. Mice lacking IRF5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1. Furthermore we found that neutrophils express little IRF5 in the joints and that their migratory properties are not affected by the IRF5 deficiency. These studies extend prior ones suggesting that inhibiting IRF5 might be useful for chronic macrophage-induced inflammation and suggest that IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury.
Blazek K, Eames HL, Weiss M, et al., 2015, IFN-lambda resolves inflammation via suppression of neutrophil infiltration and IL-1 beta production, Journal of Experimental Medicine, Vol: 212, Pages: 845-853, ISSN: 0022-1007
The most studied biological role of type III interferons (IFNs) has so far been their antiviral activity, but their role in autoimmune and inflammatory diseases remains largely unexplored. Here, we show that treatment with IFN-λ2/IL-28A completely halts and reverses the development of collagen-induced arthritis (CIA) and discover cellular and molecular mechanisms of IL-28A antiinflammatory function. We demonstrate that treatment with IL-28A dramatically reduces numbers of proinflammatory IL-17–producing Th17 and γδ T cells in the joints and inguinal lymph nodes, without affecting T cell proliferative responses or levels of anticollagen antibodies. IL-28A exerts its antiinflammatory effect by restricting recruitment of IL-1b–expressing neutrophils, which are important for amplification of inflammation. We identify neutrophils as cells expressing high levels of IFN-λ receptor 1 (IFNLR1)–IL-28 receptor α (IL28RA) and targeted by IL-28A. Our data highlight neutrophils as contributors to the pathogenesis of autoimmune arthritis and present IFN-λs or agonists of IFNLR1–IL28RA as putative new therapeutics for neutrophil-driven inflammation.IFN-λ1, -λ2, and -λ3 (or IL-29, IL-28A, and IL-28B, respectively) are members of the class II cytokine family evolutionarily related to both IL-10 and type I IFNs (IFN-α/β), and are collectively referred to as type III IFNs. IFN-λ1 (IL-29) is the main cytokine of this family produced in human cells, but it is not expressed in mice, where IL-28A/B play the major role. Despite the use of a distinct receptor complex, IFNLR1–IL28RA activates similar signaling pathways to that of the type I IFN receptor (Kotenko et al., 2003; Sheppard et al., 2003), and the most studied biological role of IFN-λs has so far been their antiviral activity. However, there is evidence to suggest that they may also have pleiotropic immune functions. IF
Lee DC, Walker SA, Byrne AJ, et al., 2015, Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life., Thorax, ISSN: 1468-3296
Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model.
Denney L, Gregory LG, Shea TJ, et al., 2014, Pulmonary epithelial-derived TGF-β1 is critical for the inception of innate lymphoid cell mediated allergic airways disease, Publisher: WILEY-BLACKWELL, Pages: 41-41, ISSN: 0019-2805
Saliba DG, Heger A, Eames HL, et al., 2014, IRF5:RelA Interaction Targets Inflammatory Genes in Macrophages, CELL REPORTS, Vol: 8, Pages: 1308-1317, ISSN: 2211-1247
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- Citations: 78
Denney L, Byrne AJ, Saglani S, et al., 2013, GATA3 expressing innate lymphoid cells are an important early source of Th2 cytokines driving allergen induced inflammation and AHR, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 90-90, ISSN: 0019-2805
Wechsler JB, Schroeder HA, Byrne AJ, et al., 2013, Anaphylactic responses to histamine in mice utilize both histamine receptors 1 and 2, ALLERGY, Vol: 68, Pages: 1338-1340, ISSN: 0105-4538
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- Citations: 22
Byrne A, Lloyd C, Walker S, et al., 2013, Overexpression of IRF5 ameliorates house dust mite-mediated airway hyper-responsiveness via macrophage polarisation towards a classically activated phenotype, EUROPEAN RESPIRATORY JOURNAL, Vol: 42, ISSN: 0903-1936
Byrne AJ, Jones CP, Gowers K, et al., 2013, Lung Macrophages Contribute to House Dust Mite Driven Airway Remodeling via HIF-1α, PLOS ONE, Vol: 8, ISSN: 1932-6203
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- Citations: 26
Weiss M, Blazek K, Byrne AJ, et al., 2013, IRF5 Is a Specific Marker of Inflammatory Macrophages <i>In Vivo</i>, MEDIATORS OF INFLAMMATION, Vol: 2013, ISSN: 0962-9351
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- Citations: 89
Swartzendruber JA, Byrne AJ, Bryce PJ, 2012, Cutting Edge: Histamine Is Required for IL-4-Driven Eosinophilic Allergic Responses, JOURNAL OF IMMUNOLOGY, Vol: 188, Pages: 536-540, ISSN: 0022-1767
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- Citations: 8
Smarr CB, Hsu C-L, Byrne AJ, et al., 2011, Antigen-Fixed Leukocytes Tolerize Th2 Responses in Mouse Models of Allergy, JOURNAL OF IMMUNOLOGY, Vol: 187, Pages: 5090-5098, ISSN: 0022-1767
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- Citations: 61
Barlow JW, Zhang T, Woods O, et al., 2011, Novel Mast Cell-Stabilising Amine Derivatives of 3,4-Dihydronaphthalen-1(2<i>H</i>)-one and 6,7,8,9-Tetrahydro-5<i>H</i>-benzo[7]annulen-5-one, MEDICINAL CHEMISTRY, Vol: 7, Pages: 213-223, ISSN: 1573-4064
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- Citations: 18
Byrne AJ, Barlow JW, Walsh JJ, 2011, Synthesis and pharmacological evaluation of the individual stereoisomers of 3-[methyl(1,2,3,4-tetrahydro-2-naphthalenyl)amino]-1-indanone, a potent mast cell stabilising agent, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, Vol: 21, Pages: 1191-1194, ISSN: 0960-894X
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- Citations: 8
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