Publications
250 results found
Ombredane HCJ, Fenwick PS, Barnes PJ, et al., 2023, Temporal Release of IL-1 Family Members from Virally Infected Airway Epithelial Cells Suggests IL-36γ Is the Early Responder., Am J Respir Cell Mol Biol, Vol: 68, Pages: 339-341
Fawzy A, Baker JR, Keller TL, et al., 2022, Selected Bibliography of Recent Research in Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 206, Pages: 1408-1417, ISSN: 1073-449X
Wrench C, Dodgson J, Overed-Sayer C, et al., 2022, Role of urokinase-type plasminogen activator receptor (uPAR) in senescent lung cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Devulder J, Baker JR, Odqvist L, et al., 2022, Extracellular vesicles propagate cellular senescence by transferring miR34a in airway epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Ho V, Baker JR, Willison KR, et al., 2022, An amplification-free, innovative, multiplex assay to quantify microRNAs in single cells from COPD patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Hassibi S, Baker J, Barnes P, et al., 2022, COPD Monocyte-derived macrophages display hallmarks of senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Baker JR, Fenwick PS, Koss CK, et al., 2022, Imbalance between IL-36 receptor agonist and antagonist drives neutrophilic inflammation in COPD, JCI Insight, Vol: 7, ISSN: 2379-3708
Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating alternative therapies. Here, we show that COPD subjects have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared to control subjects. IL-36γ is derived from small airway epithelial cells (SAEC) and further induced by a viral mimetic, whereas IL-36RA is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, that was inhibited by exogenous IL-36RA. The use of a therapeutic antibody that inhibits binding to the IL-36 receptor (IL-36R) attenuated IL-36γ driven inflammation and cellular cross talk. We have demonstrated a mechanism for the amplification and propagation of neutrophilic inflammation in COPD and that blocking this cytokine family via a IL-36R neutralizing antibody could be a promising new therapeutic strategy in the treatment of COPD.
Tsu M, Genton C, Saglani S, et al., 2022, ERS scientific awards: striving for inclusivity, EUROPEAN RESPIRATORY JOURNAL, Vol: 60, ISSN: 0903-1936
Devulder J, Baker JR, Odqvist L, et al., 2022, Transfer of microRNA Through Extracellular Vesicles Propagate Airway Epithelial Cells Senescence in COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Baker JR, Fenwick PS, Koss CK, et al., 2022, Inhibition of the IL-36 Receptor Reduces Viral Induced Cross-Talk Between Small Airway Epithelial Cells and Fibroblast in COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Ho V, Baker JR, Willison KR, et al., 2022, Novel Single Cell Analysis of microRNA Levels in Response to Oxidative Stress and in COPD Using Microfluidic Technology, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Fenwick P, Baker JR, Koss CK, et al., 2022, TRPV4 Identifies Phagocytic Macrophages and May Promote Phagocytosis in Both Healthy and COPD Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Hassibi S, Baker JR, Barnes PJ, et al., 2022, COPD Macrophages Show Reduced Clearance of Senescent Airway Epithelial Cells, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Wysoczanski R, Baker JR, Fenwick P, et al., 2022, Defective Phagocytosis in COPD Macrophages Is Improved by Mitochondrial Antioxidants Without Alteration in Mitochondrial Function, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Barnes PJ, Baker J, Donnelly LE, 2022, Autophagy in asthma and chronic obstructive pulmonary disease, CLINICAL SCIENCE, Vol: 136, Pages: 733-746, ISSN: 0143-5221
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- Citations: 5
Baker JR, Mahdi M, Nicolau DV, et al., 2022, Early Th2 inflammation in the upper respiratory mucosa as a predictor of severe COVID-19 and modulation by early treatment with inhaled corticosteroids: a mechanistic analysis., The Lancet Respiratory Medicine, ISSN: 2213-2600
BACKGROUND: Community-based clinical trials of the inhaled corticosteroid budesonide in early COVID-19 have shown improved patient outcomes. We aimed to understand the inflammatory mechanism of budesonide in the treatment of early COVID-19. METHODS: The STOIC trial was a randomised, open label, parallel group, phase 2 clinical intervention trial where patients were randomly assigned (1:1) to receive usual care (as needed antipyretics were only available treatment) or inhaled budesonide at a dose of 800 μg twice a day plus usual care. For this experimental analysis, we investigated the nasal mucosal inflammatory response in patients recruited to the STOIC trial and in a cohort of SARS-CoV-2-negative healthy controls, recruited from a long-term observational data collection study at the University of Oxford. In patients with SARS-CoV-2 who entered the STOIC study, nasal epithelial lining fluid was sampled at day of randomisation (day 0) and at day 14 following randomisation, blood samples were also collected at day 28 after randomisation. Nasal epithelial lining fluid and blood samples were collected from the SARS-CoV-2 negative control cohort. Inflammatory mediators in the nasal epithelial lining fluid and blood were assessed for a range of viral response proteins, and innate and adaptive response markers using Meso Scale Discovery enzyme linked immunoassay panels. These samples were used to investigate the evolution of inflammation in the early COVID-19 disease course and assess the effect of budesonide on inflammation. FINDINGS: 146 participants were recruited in the STOIC trial (n=73 in the usual care group; n=73 in the budesonide group). 140 nasal mucosal samples were available at day 0 (randomisation) and 122 samples at day 14. At day 28, whole blood was collected from 123 participants (62 in the budesonide group and 61 in the usual care group). 20 blood or nasal samples were collected from healthy controls. In early COVID-19 disease, there was an enhanced in
Koss CK, Wohnhaas CT, Baker JR, et al., 2021, IL36 is a critical upstream amplifier of neutrophilic lung inflammation in mice, Communications Biology, Vol: 4, Pages: 1-15, ISSN: 2399-3642
IL-36, which belongs to the IL-1 superfamily, is increasingly linked to neutrophilic inflammation. Here, we combined in vivo and in vitro approaches using primary mouse and human cells, as well as, acute and chronic mouse models of lung inflammation to provide mechanistic insight into the intercellular signaling pathways and mechanisms through which IL-36 promotes lung inflammation. IL-36 receptor deficient mice exposed to cigarette smoke or cigarette smoke and H1N1 influenza virus had attenuated lung inflammation compared with wild-type controls. We identified neutrophils as a source of IL-36 and show that IL-36 is a key upstream amplifier of lung inflammation by promoting activation of neutrophils, macrophages and fibroblasts through cooperation with GM-CSF and the viral mimic poly(I:C). Our data implicate IL-36, independent of other IL-1 family members, as a key upstream amplifier of neutrophilic lung inflammation, providing a rationale for targeting IL-36 to improve treatment of a variety of neutrophilic lung diseases.
van den Berge M, Genton C, Heuvelin E, et al., 2021, Success and continuous growth of the ERS clinical research collaborations, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936
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- Citations: 2
Wysoczanski R, Baker J, Fenwick P, et al., 2021, Image analysis of tissue macrophages to confirm differential phagocytosis between groups by microscopy and automated bacterial quantification, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Baker JR, Fenwick PS, Owles HB, et al., 2021, IL-36? - a key mediator of neutrophilic inflammation in chronic obstructive pulmonary disease, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Ho V, Willison K, Baker J, et al., 2021, Microfluidic single cell analysis of microRNA levels in small airway epithelial cells and fibroblasts from COPD patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Hassibi S, Baker J, Barnes P, et al., 2021, Generating senescent airway epithelial cell populations using low-concentration doxorubicin or etoposide, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Devulder J, Baker JR, Donnelly LE, et al., 2021, Extracellular vesicles produced by airway epithelial cells in response to oxidative stress contain microRNAs associated with cellular senescence, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Lightley J, Gorlitz F, Kumar S, et al., 2021, Robust deep learning optical autofocus system applied to automated multiwell plate single molecule localization microscopy, JOURNAL OF MICROSCOPY, ISSN: 0022-2720
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- Citations: 1
Baker JR, Donnelly LE, 2021, Leukocyte function in COPD: clinical relevance and potential for drug therapy., The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 16, Pages: 2227-2242, ISSN: 1176-9106
Chronic obstructive pulmonary disease (COPD) is a progressive lung condition affecting 10% of the global population over 45 years. Currently, there are no disease-modifying treatments, with current therapies treating only the symptoms of the disease. COPD is an inflammatory disease, with a high infiltration of leukocytes being found within the lung of COPD patients. These leukocytes, if not kept in check, damage the lung, leading to the pathophysiology associated with the disease. In this review, we focus on the main leukocytes found within the COPD lung, describing how the release of chemokines from the damaged epithelial lining recruits these cells into the lung. Once present, these cells become active and may be driven towards a more pro-inflammatory phenotype. These cells release their own subtypes of inflammatory mediators, growth factors and proteases which can all lead to airway remodeling, mucus hypersecretion and emphysema. Finally, we describe some of the current therapies and potential new targets that could be utilized to target aberrant leukocyte function in the COPD lung. Here, we focus on old therapies such as statins and corticosteroids, but also look at the emerging field of biologics describing those which have been tested in COPD already and potential new monoclonal antibodies which are under review.
Ritchie AI, Baker JR, Parekh TM, et al., 2021, Update in Chronic Obstructive Pulmonary Disease 2020, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 204, Pages: 14-22, ISSN: 1073-449X
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- Citations: 5
Ramakrishnan S, Nicolau D, Langford B, et al., 2021, Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial, LANCET RESPIRATORY MEDICINE, Vol: 9, Pages: 763-772, ISSN: 2213-2600
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- Citations: 187
Singh R, Belchamber K, Fenwick P, et al., 2021, Defective monocyte-derived macrophage phagocytosis is associated with exacerbation frequency in COPD, Respiratory Research, Vol: 22, Pages: 1-11, ISSN: 1465-9921
BackgroundLower airway bacterial colonisation (LABC) in COPD patients is associated with increased exacerbation frequency and faster lung function decline. Defective macrophage phagocytosis in COPD drives inflammation, but how defective macrophage function contributes to exacerbations is not clear. This study investigated the association between macrophage phagocytosis and exacerbation frequency, LABC and clinical parameters.MethodsMonocyte-derived macrophages (MDM) were generated from 92 stable COPD patients, and at the onset of exacerbation in 39 patients. Macrophages were exposed to fluorescently labelled Haemophilus influenzae or Streptococcus pneumoniae for 4 h, then phagocytosis measured by fluorimetry and cytokine release by ELISA. Sputum bacterial colonisation was measured by PCR.ResultsPhagocytosis of H. influenzae was negatively correlated with exacerbation frequency (r = 0.440, p < 0.01), and was significantly reduced in frequent vs. infrequent exacerbators (1.9 × 103 RFU vs. 2.5 × 103 RFU, p < 0.01). There was no correlation for S. pneumoniae. There was no association between phagocytosis of either bacteria with age, lung function, smoking history or treatment with inhaled corticosteroids, or long-acting bronchodilators. Phagocytosis was not altered during an exacerbation, or in the 2 weeks post-exacerbation. In response to phagocytosis, MDM from exacerbating patients showed increased release of CXCL-8 (p < 0.001) and TNFα (p < 0.01) compared to stable state.ConclusionImpaired COPD macrophage phagocytosis of H. influenzae, but not S. pneumoniae is associated with exacerbation frequency, resulting in pro-inflammatory macrophages that may contribute to disease progression. Targeting these frequent exacerbators with drugs that improve macrophage phagocytosis may prove beneficial.
Perez E, Baker JR, Di Giandomenico S, et al., 2020, Hepcidin Is Essential for Alveolar Macrophage Function and Is Disrupted by Smoke in a Murine Chronic Obstructive Pulmonary Disease Model, JOURNAL OF IMMUNOLOGY, Vol: 205, Pages: 2489-+, ISSN: 0022-1767
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- Citations: 8
Baker JR, Fenwick PS, Donnelly L, et al., 2020, Altered iron metabolism and elevated cellular senescence in COPD small airway epithelial cells, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
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