Donovan, C, Starkey, MR, Kim, RY, Rana, BMJ, Barlow, JL, Jones, B, Haw, TJ, Mono Nair, P, Budden, K, Cameron, GJM, Horvat, JC, Wark, PA, Foster, PS, McKenzie, ANJ & Hansbro, PM 2019, 'Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease.', Journal of leukocyte biology, vol. 105, no. 1, pp. 143-150.View/Download from: UTS OPUS or Publisher's site
Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and lung function in an experimental model of COPD using mice that specifically lack these cells (Rag1-/- and Rorafl/fl Il7rCre [ILC2-deficient] mice). Wild-type (WT) C57BL/6 mice, Rag1-/- , and Rorafl/fl Il7rCre mice were exposed to cigarette smoke (CS; 12 cigarettes twice a day, 5 days a week) for up to 12 weeks, and airway inflammation, airway remodelling (collagen deposition and alveolar enlargement), and lung function were assessed. WT, Rag1-/- , and ILC2-deficient mice exposed to CS had similar levels of airway inflammation and impaired lung function. CS exposure increased small airway collagen deposition in WT mice. Rag1-/- normal air- and CS-exposed mice had significantly increased collagen deposition compared to similarly exposed WT mice, which was associated with increases in IL-33, IL-13, and ILC2 numbers. CS-exposed Rorafl/fl Il7rCre mice were protected from emphysema, but had increased IL-33/IL-13 expression and collagen deposition compared to WT CS-exposed mice. T/B lymphocytes and ILC2s play roles in airway collagen deposition/fibrosis, but not inflammation, in experimental COPD.
Keenan, CR, Iannarella, N, Garnham, AL, Brown, AC, Kim, RY, Horvat, JC, Hansbro, PM, Nutt, SL & Allan, RS 2019, 'Polycomb repressive complex 2 is a critical mediator of allergic inflammation.', JCI insight, vol. 4, no. 10.View/Download from: UTS OPUS or Publisher's site
Strategies that intervene with the development of immune-mediated diseases are urgently needed, as current treatments mostly focus on alleviating symptoms rather than reversing the disease. Targeting enzymes involved in epigenetic modifications to chromatin represents an alternative strategy that has the potential to perturb the function of the lymphocytes that drive the immune response. Here, we report that 2 major epigenetic silencing pathways are increased after T cell activation. By specific inactivation of these molecules in the T cell compartment in vivo, we demonstrate that the polycomb repressive complex 2 (PRC2) is essential for the generation of allergic responses. Furthermore, we show that small-molecule inhibition of the PRC2 methyltransferase, enhancer of zeste homolog 2 (Ezh2), reduces allergic inflammation in mice. Therefore, by systematically surveying the pathways involved in epigenetic gene silencing we have identified Ezh2 as a target for the suppression of allergic disease.
Starkey, MR, Plank, MW, Casolari, P, Papi, A, Pavlidis, S, Guo, Y, Cameron, GJM, Haw, TJ, Tam, A, Obiedat, M, Donovan, C, Hansbro, NG, Nguyen, DH, Nair, PM, Kim, RY, Horvat, JC, Kaiko, GE, Durum, SK, Wark, PA, Sin, DD, Caramori, G, Adcock, IM, Foster, PS & Hansbro, PM 2019, 'IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis', EUROPEAN RESPIRATORY JOURNAL, vol. 54, no. 1.View/Download from: UTS OPUS or Publisher's site
Wadhwa, R, Dua, K, Adcock, IM, Horvat, JC, Kim, RY & Hansbro, PM 2019, 'Cellular mechanisms underlying steroid-resistant asthma.', European respiratory review : an official journal of the European Respiratory Society, vol. 28, no. 153.View/Download from: UTS OPUS or Publisher's site
Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.
Fricker, M, Goggins, BJ, Mateer, S, Jones, B, Kim, RY, Gellatly, SL, Jarnicki, AG, Powell, N, Oliver, BG, Radford-Smith, G, Talley, NJ, Walker, MM, Keely, S & Hansbro, PM 2018, 'Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction.', JCI insight, vol. 3, no. 3.View/Download from: UTS OPUS or Publisher's site
Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract (GIT). Cigarette smoke (CS) exposure and chronic obstructive pulmonary disease (COPD) are risk factors for CD, although the mechanisms involved are poorly understood. We employed a mouse model of CS-induced experimental COPD and clinical studies to examine these mechanisms. Concurrent with the development of pulmonary pathology and impaired gas exchange, CS-exposed mice developed CD-associated pathology in the colon and ileum, including gut mucosal tissue hypoxia, HIF-2 stabilization, inflammation, increased microvasculature, epithelial cell turnover, and decreased intestinal barrier function. Subsequent smoking cessation reduced GIT pathology, particularly in the ileum. Dimethyloxaloylglycine, a pan-prolyl hydroxylase inhibitor, ameliorated CS-induced GIT pathology independently of pulmonary pathology. Prior smoke exposure exacerbated intestinal pathology in 2,4,6-trinitrobenzenesulfonic acid-induced (TNBS-induced) colitis. Circulating vascular endothelial growth factor, a marker of systemic hypoxia, correlated with CS exposure and CD in mice and humans. Increased mucosal vascularisation was evident in ileum biopsies from CD patients who smoke compared with nonsmokers, supporting our preclinical data. We provide strong evidence that chronic CS exposure and, for the first time to our knowledge, associated impaired gas exchange cause systemic and intestinal ischemia, driving angiogenesis and GIT epithelial barrier dysfunction, resulting in increased risk and severity of CD.
Haw, TJ, Starkey, MR, Pavlidis, S, Fricker, M, Arthurs, AL, Nair, PM, Liu, G, Hanish, I, Kim, RY, Foster, PS, Horvat, JC, Adcock, IM & Hansbro, PM 2018, 'Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease', AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, vol. 314, no. 2, pp. L298-L317.View/Download from: UTS OPUS or Publisher's site
Mateer, SW, Mathe, A, Bruce, J, Liu, G, Maltby, S, Fricker, M, Goggins, BJ, Tay, HL, Marks, E, Burns, G, Kim, RY, Minahan, K, Walker, MM, Callister, RC, Foster, PS, Horvat, JC, Hansbro, PM & Keely, S 2018, 'IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis.', The American journal of pathology, vol. 188, no. 7, pp. 1625-1639.View/Download from: UTS OPUS or Publisher's site
Inflammatory bowel disease (IBD) is associated with several immune-mediated extraintestinal manifestations. More than half of all IBD patients have some form of respiratory pathology, most commonly neutrophil-mediated diseases, such as bronchiectasis and chronic bronchitis. Using murine models of colitis, we aimed to identify the immune mechanisms driving pulmonary manifestations of IBD. We found increased neutrophil numbers in lung tissue associated with the pulmonary vasculature in both trinitrobenzenesulfonic acid- and dextran sulfate sodium-induced models of colitis. Analysis of systemic inflammation identified that neutrophilia was associated with bacteremia and pyrexia in animal models of colitis. We further identified IL-6 as a systemic mediator of neutrophil recruitment from the bone marrow of dextran sulfate sodium animals. Functional inhibition of IL-6 led to reduced systemic and pulmonary neutrophilia, but it did not attenuate established colitis pathology. These data suggest that systemic bacteremia and pyrexia drive IL-6 secretion, which is a critical driver for pulmonary manifestation of IBD. Targeting IL-6 may reduce neutrophil-associated extraintestinal manifestations in IBD patients.
Ali, MK, Kim, RY, Karim, R, Mayall, JR, Martin, KL, Shahandeh, A, Abbasian, F, Starkey, MR, Loustaud-Ratti, V, Johnstone, D, Milward, EA, Hansbro, PM & Horvat, JC 2017, 'Role of iron in the pathogenesis of respiratory disease.', The International Journal of Biochemistry & Cell Biology, vol. 88, pp. 181-195.View/Download from: UTS OPUS or Publisher's site
Iron is essential for many biological processes, however, too much or too little iron can result in a wide variety of pathological consequences, depending on the organ system, tissue or cell type affected. In order to reduce pathogenesis, iron levels are tightly controlled in throughout the body by regulatory systems that control iron absorption, systemic transport and cellular uptake and storage. Altered iron levels and/or dysregulated homeostasis have been associated with several lung diseases, including chronic obstructive pulmonary disease, lung cancer, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. However, the mechanisms that underpin these associations and whether iron plays a key role in the pathogenesis of lung disease are yet to be fully elucidated. Furthermore, in order to survive and replicate, pathogenic micro-organisms have evolved strategies to source host iron, including freeing iron from cells and proteins that store and transport iron. To counter these microbial strategies, mammals have evolved immune-mediated defence mechanisms that reduce iron availability to pathogens. This interplay between iron, infection and immunity has important ramifications for the pathogenesis and management of human respiratory infections and diseases. An increased understanding of the role that iron plays in the pathogenesis of lung disease and respiratory infections may help inform novel therapeutic strategies. Here we review the clinical and experimental evidence that highlights the potential importance of iron in respiratory diseases and infections.
Conickx, G, Mestdagh, P, Avila Cobos, F, Verhamme, FM, Maes, T, Vanaudenaerde, BM, Seys, LJM, Lahousse, L, Kim, RY, Hsu, AC, Wark, PA, Hansbro, PM, Joos, GF, Vandesompele, J, Bracke, KR & Brusselle, GG 2017, 'MicroRNA Profiling Reveals a Role for MicroRNA-218-5p in the Pathogenesis of Chronic Obstructive Pulmonary Disease.', American Journal of Respiratory and Critical Care Medicine, vol. 195, no. 1, pp. 43-56.View/Download from: UTS OPUS or Publisher's site
Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis.To identify dysregulated miRNAs in lung tissue of patients with chronic obstructive pulmonary disease (COPD).We performed miRNA and mRNA profiling using high throughput stem-loop reverse-transcriptase quantitative polymerase chain reaction and mRNA microarray, respectively, on lung tissue of 30 patients (screening cohort) encompassing 8 never-smokers, 10 smokers without airflow limitation, and 12 smokers with COPD. Differential expression of miRNA-218-5p (miR-218-5p) was validated by reverse-transcriptase quantitative polymerase chain reaction in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis.Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD compared with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD.We highlight a role for miR-218-5p in the pathogenesis of COPD.
Eapen, MS, Hansbro, PM, McAlinden, K, Kim, RY, Ward, C, Hackett, T-L, Walters, EH & Sohal, SS 2017, 'Abnormal M1/M2 macrophage phenotype profiles in the small airway wall and lumen in smokers and chronic obstructive pulmonary disease (COPD).', Scientific reports, vol. 7, no. 1, pp. 13392-13392.View/Download from: UTS OPUS or Publisher's site
We explore potential dysregulation of macrophage phenotypes in COPD pathogenesis through integrated study of human small airway tissue, bronchoalveolar lavage (BAL) and an experimental murine model of COPD. We evaluated human airway tissue and BAL from healthy controls, normal lung function smokers (NLFS), and COPD subjects. Both small airways and BAL cells were immunohistochemically stained with anti-CD68 for total macrophages and with anti-CD163 for M2, and anti-iNOS for M1 macrophages. Multiplex ELISA measured BAL cytokines. Comparable cigarette smoke-induced experimental COPD mouse model was assessed for relevant mRNA profiles. We found an increase in pro-inflammatory M1s in the small airways of NLFS and COPD compared to controls with a reciprocal decrease in M2 macrophages, which remained unchanged among pathological groups. However, luminal macrophages showed a dominant M2 phenotype in both NLFS and COPD subjects. BAL cytokine skewed towards an M2 profile with increase in CCL22, IL-4, IL-13, and IL-10 in both NLFS and COPDs. The mouse-model of COPD showed similar increase in mRNA for M2 markers. Our finding suggests abnormal macrophage switching in both mucosal and luminal areas of COPD patients, that strongly associated with cytokine balance. There may be potential for beneficial therapeutic cytokine manipulation of macrophage phenotypes in COPD.
Hansbro, PM, Kim, RY, Starkey, MR, Donovan, C, Dua, K, Mayall, JR, Liu, G, Hansbro, NG, Simpson, JL, Wood, LG, Hirota, JA, Knight, DA, Foster, PS & Horvat, JC 2017, 'Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma.', Immunological reviews, vol. 278, no. 1, pp. 41-62.View/Download from: UTS OPUS or Publisher's site
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.
Kim, RY, Horvat, JC, Pinkerton, JW, Starkey, MR, Essilfie, AT, Mayall, JR, Nair, PM, Hansbro, NG, Jones, B, Haw, TJ, Sunkara, KP, Nguyen, TH, Jarnicki, AG, Keely, S, Mattes, J, Adcock, IM, Foster, PS & Hansbro, PM 2017, 'MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2.', Journal of Allergy and Clinical Immunology, vol. 139, no. 2, pp. 519-532.View/Download from: UTS OPUS or Publisher's site
Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease.We sought to develop representative mouse models of severe, steroid-insensitive asthma and to use them to identify pathogenic mechanisms and investigate new treatment approaches.Novel mouse models of Chlamydia, Haemophilus influenzae, influenza, and respiratory syncytial virus respiratory tract infections and ovalbumin-induced, severe, steroid-insensitive allergic airway disease (SSIAAD) in BALB/c mice were developed and interrogated.Infection induced increases in the levels of microRNA (miRNA)-21 (miR-21) expression in the lung during SSIAAD, whereas expression of the miR-21 target phosphatase and tensin homolog was reduced. This was associated with an increase in levels of phosphorylated Akt, an indicator of phosphoinositide 3-kinase (PI3K) activity, and decreased nuclear histone deacetylase (HDAC)2 levels. Treatment with an miR-21-specific antagomir (Ant-21) increased phosphatase and tensin homolog levels. Treatment with Ant-21, or the pan-PI3K inhibitor LY294002, reduced PI3K activity and restored HDAC2 levels. This led to suppression of airway hyperresponsiveness and restored steroid sensitivity to allergic airway disease. These observations were replicated with SSIAAD associated with 4 different pathogens.We identify a previously unrecognized role for an miR-21/PI3K/HDAC2 axis in SSIAAD. Our data highlight miR-21 as a novel therapeutic target for the treatment of t...
Kim, RY, Pinkerton, JW, Essilfie, AT, Robertson, AAB, Baines, KJ, Brown, AC, Mayall, JR, Ali, MK, Starkey, MR, Hansbro, NG, Hirota, JA, Wood, LG, Simpson, JL, Knight, DA, Wark, PA, Gibson, PG, O'Neill, LAJ, Cooper, MA, Horvat, JC & Hansbro, PM 2017, 'Role for NLRP3 Inflammasome-mediated, IL-1β-Dependent Responses in Severe, Steroid-Resistant Asthma.', American Journal of Respiratory and Critical Care Medicine, vol. 196, no. 3, pp. 283-297.View/Download from: UTS OPUS or Publisher's site
Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma.To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1β in severe, steroid-resistant asthma.We developed mouse models of Chlamydia and Haemophilus respiratory infection-mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including elevated airway neutrophils, and NLRP3 inflammasome and IL-1β responses. The roles and potential for targeting of NLRP3 inflammasome, caspase-1, and IL-1β responses in experimental severe, steroid-resistant asthma were examined using a highly selective NLRP3 inhibitor, MCC950; the specific caspase-1 inhibitor Ac-YVAD-cho; and neutralizing anti-IL-1β antibody. Roles for IL-1β-induced neutrophilic inflammation were examined using IL-1β and anti-Ly6G.Chlamydia and Haemophilus infections increase NLRP3, caspase-1, IL-1β responses that drive steroid-resistant neutrophilic inflammation and airway hyperresponsiveness. Neutrophilic airway inflammation, disease severity, and steroid resistance in human asthma correlate with NLRP3 and IL-1β expression. Treatment with anti-IL-1β, Ac-YVAD-cho, and MCC950 suppressed IL-1β responses and the important steroid-resistant features of disease in mice, whereas IL-1β administration recapitulated these features. Neutrophil depletion suppressed IL-1β-induced steroid-res...
Pinkerton, JW, Kim, RY, Robertson, AAB, Hirota, JA, Wood, LG, Knight, DA, Cooper, MA, O'Neill, LAJ, Horvat, JC & Hansbro, PM 2017, 'Inflammasomes in the lung', Molecular Immunology, vol. 86, pp. 44-55.View/Download from: UTS OPUS or Publisher's site
Innate immune responses act as first line defences upon exposure to potentially noxious stimuli. The innate immune system has evolved numerous intracellular and extracellular receptors that undertake surveillance for potentially damaging particulates. Inflammasomes are intracellular innate immune multiprotein complexes that form and are activated following interaction with these stimuli. Inflammasome activation leads to the cleavage of pro-IL-1β and release of the pro-inflammatory cytokine, IL-1β, which initiates acute phase pro-inflammatory responses, and other responses are also involved (IL-18, pyroptosis). However, excessive activation of inflammasomes can result in chronic inflammation, which has been implicated in a range of chronic inflammatory diseases. The airways are constantly exposed to a wide variety of stimuli. Inflammasome activation and downstream responses clears these stimuli. However, excessive activation may drive the pathogenesis of chronic respiratory diseases such as severe asthma and chronic obstructive pulmonary disease. Thus, there is currently intense interest in the role of inflammasomes in chronic inflammatory lung diseases and in their potential for therapeutic targeting. Here we review the known associations between inflammasome-mediated responses and the development and exacerbation of chronic lung diseases.
Haw, TJ, Starkey, MR, Nair, PM, Pavlidis, S, Liu, G, Nguyen, DH, Hsu, AC, Hanish, I, Kim, RY, Collison, AM, Inman, MD, Wark, PA, Foster, PS, Knight, DA, Mattes, J, Yagita, H, Adcock, IM, Horvat, JC & Hansbro, PM 2016, 'A pathogenic role for tumor necrosis factor-related apoptosis-inducing ligand in chronic obstructive pulmonary disease', MUCOSAL IMMUNOLOGY, vol. 9, no. 4, pp. 859-872.View/Download from: Publisher's site
Starkey, MR, Nguyen, DH, Brown, AC, Essilfie, A-T, Kim, RY, Yagita, H, Horvat, JC & Hansbro, PM 2016, 'Programmed Death Ligand 1 Promotes Early-Life Chlamydia Respiratory Infection-Induced Severe Allergic Airway Disease', AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, vol. 54, no. 4, pp. 493-503.View/Download from: Publisher's site
Essilfie, A-T, Horvat, JC, Kim, RY, Mayall, JR, Pinkerton, JW, Beckett, EL, Starkey, MR, Simpson, JL, Foster, PS, Gibson, PG & Hansbro, PM 2015, 'Macrolide therapy suppresses key features of experimental steroid-sensitive and steroid-insensitive asthma', THORAX, vol. 70, no. 5, pp. 458-U151.View/Download from: Publisher's site
Kim, RY, Pinkerton, JW, Gibson, PG, Cooper, MA, Horvat, JC & Hansbro, PM 2015, 'Inflammasomes in COPD and neutrophilic asthma', THORAX, vol. 70, no. 12, pp. 1199-1201.View/Download from: Publisher's site
Starkey, MR, Nguyen, DH, Essilfie, AT, Kim, RY, Hatchwell, LM, Collison, AM, Yagita, H, Foster, PS, Horvat, JC, Mattes, J & Hansbro, PM 2014, 'Tumor necrosis factor-related apoptosis-inducing ligand translates neonatal respiratory infection into chronic lung disease', MUCOSAL IMMUNOLOGY, vol. 7, no. 3, pp. 478-488.View/Download from: Publisher's site
Beckett, EL, Stevens, RL, Jarnicki, AG, Kim, RY, Hanish, I, Hansbro, NG, Deane, A, Keely, S, Horvat, JC, Yang, M, Oliver, BG, van Rooijen, N, Inman, MD, Adachi, R, Soberman, RJ, Hamadi, S, Wark, PA, Foster, PS & Hansbro, PM 2013, 'A new short-term mouse model of chronic obstructive pulmonary disease identifies a role for mast cell tryptase in pathogenesis', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 131, no. 3, pp. 752-+.View/Download from: UTS OPUS or Publisher's site
Hansbro, PM, Scott, GV, Essilfie, A-T, Kim, RY, Starkey, MR, Nguyen, DH, Allen, PD, Kaiko, GE, Yang, M, Horvat, JC & Foster, PS 2013, 'Th2 cytokine antagonists: potential treatments for severe asthma', EXPERT OPINION ON INVESTIGATIONAL DRUGS, vol. 22, no. 1, pp. 49-69.View/Download from: Publisher's site
Starkey, MR, Essilfie, AT, Horvat, JC, Kim, RY, Nguyen, DH, Beagley, KW, Mattes, J, Foster, PS & Hansbro, PM 2013, 'Constitutive production of IL-13 promotes early-life Chlamydia respiratory infection and allergic airway disease', MUCOSAL IMMUNOLOGY, vol. 6, no. 3, pp. 569-579.View/Download from: Publisher's site
Starkey, MR, Jarnicki, AG, Essilfie, A-T, Gellatly, SL, Kim, RY, Brown, AC, Foster, PS, Horvat, JC & Hansbro, PM 2013, 'Murine models of infectious exacerbations of airway inflammation', CURRENT OPINION IN PHARMACOLOGY, vol. 13, no. 3, pp. 337-344.View/Download from: Publisher's site
Starkey, MR, Nguyen, DH, Kim, RY, Nair, PM, Brown, AC, Essifie, A-T, Horvat, JC & Hansbro, PM 2013, 'Programming of the Lung in Early Life by Bacterial Infections Predisposes to Chronic Respiratory Disease', CLINICAL OBSTETRICS AND GYNECOLOGY, vol. 56, no. 3, pp. 566-576.View/Download from: Publisher's site
Hansbro, PM, Starkey, MR, Kim, RY, Stevens, RL, Foster, PS & Horvat, JC 2012, 'Programming of the lung by early-life infection', JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, vol. 3, no. 3, pp. 153-158.View/Download from: Publisher's site
Starkey, MR, Kim, RY, Beckett, EL, Schilter, HC, Shim, D, Essilfie, A-T, Nguyen, DH, Beagley, KW, Mattes, J, Mackay, CR, Horvat, JC & Hansbro, PM 2012, 'Chlamydia muridarum Lung Infection in Infants Alters Hematopoietic Cells to Promote Allergic Airway Disease in Mice', PLOS ONE, vol. 7, no. 8.View/Download from: UTS OPUS or Publisher's site
Wynne, O, Horvat, JC, Kim, RY, Ong, LK, Smith, R, Hansbro, PM, Clifton, VL & Hodgson, DM 2011, 'Neonatal respiratory infection and adult re-infection: Effect on glucocorticoid and mineralocorticoid receptors in the hippocampus in BALB/c mice', BRAIN BEHAVIOR AND IMMUNITY, vol. 25, no. 6, pp. 1214-1222.View/Download from: Publisher's site
Horvat, JC, Starkey, MR, Kim, RY, Beagley, KW, Preston, JA, Gibson, PG, Foster, PS & Hansbro, PM 2010, 'Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease', JOURNAL OF IMMUNOLOGY, vol. 184, no. 8, pp. 4159-4169.View/Download from: Publisher's site
Horvat, JC, Starkey, MR, Kim, RY, Phipps, S, Gibson, PG, Beagley, KW, Foster, PS & Hansbro, PM 2010, 'Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology', JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, vol. 125, no. 3, pp. 617-625.View/Download from: Publisher's site
Eapen, M, Hansbro, P, McAlinden, K, Kim, R, Hackett, T-L, Ward, C, Walters, H & Sohal, SS 2017, 'Abnormal M1/M2 macrophage switching in small airway wall and lumen of smokers and COPD patients', EUROPEAN RESPIRATORY JOURNAL, European-Respiratory-Society (ERS) International Congress, EUROPEAN RESPIRATORY SOC JOURNALS LTD, Milan, ITALY.View/Download from: Publisher's site
Horvat, JC, Ali, MK, Johnstone, D, Kim, RY, Mayall, JR, Karim, R, Pinkerton, JW, Heidari, M, Martin, KL, Donovam, C, Liu, G, Milward, EA & Hansbro, PM 2017, 'Role for dysregulated iron in the pathogenesis of murine models of lung disease', JOURNAL OF IMMUNOLOGY, Annual Meeting of the American-Association-of-Immunologists (AAI), AMER ASSOC IMMUNOLOGISTS, Washington, DC.
Horvat, JC, Mayall, JR, Mangan, NE, Brown, AC, Chevalier, A, Starkey, MR, Kim, RY, Hertzog, P & Hansbro, PM 2017, 'IFN-epsilon regulated innate immune responses in the female reproductive tract during Chlarnydia infection', JOURNAL OF IMMUNOLOGY, Annual Meeting of the American-Association-of-Immunologists (AAI), AMER ASSOC IMMUNOLOGISTS, Washington, DC.
Kim, RYH, Pinkerton, JW, Rae, BE, Mayall, JR, Brown, AC, Nli, MK, Goggins, BJ, Essilfie, A-T, Starkey, MR, To, C, Bosco, A, Horvat, JC & Hansbro, PM 2017, 'Impaired induction of Slc26a4 promotes respiratory acidosis and severe, steroid-resistant asthma', JOURNAL OF IMMUNOLOGY, Annual Meeting of the American-Association-of-Immunologists (AAI), AMER ASSOC IMMUNOLOGISTS, Washington, DC.
Starkey, MR, Nguyen, DH, Kim, RY, Nair, PM, Haw, T, Horvat, JC, Godfrey, DI, McKenzie, AN & Hansbro, PM 2017, 'Early-life respiratory bacterial infection-induced chronic lung disease is driven by a novel TLR2/IL-13/miR-21/PI3K-dependent, but MyD88-independent signalling pathway', JOURNAL OF IMMUNOLOGY, Annual Meeting of the American-Association-of-Immunologists (AAI), AMER ASSOC IMMUNOLOGISTS, Washington, DC.
Horvat, J, Kim, R, Pinkerton, J, Essilfie, A-T, Robertson, A, Baines, K, Mayall, J, Starkey, M, Wark, P, Gibson, P, O'Neill, L, Cooper, M & Hansbro, P 2016, 'NLRP3 inflammasome-mediated, IL-1 beta-dependent inflammatory responses drive steroid-resistant asthma', EUROPEAN RESPIRATORY JOURNAL, EUROPEAN RESPIRATORY SOC JOURNALS LTD.View/Download from: Publisher's site
Horvat, J, Kim, R, Pinkerton, J, Rae, B, Starkey, M, Essilfie, A-T, Mayall, J, Jones, B, Haw, TJ, Hiep, N, Keely, S, Mattes, J, Adcock, I, Foster, P & Hansbro, P 2016, 'Identification of therapeutic targets for steroid-insensitive asthma using models that represent different clinical subtypes of disease', EUROPEAN RESPIRATORY JOURNAL, EUROPEAN RESPIRATORY SOC JOURNALS LTD.View/Download from: Publisher's site