2023 |
Sikder MAA, Rashid RB, Ahmed T, Sebina I, Howard DR, Ullah MA, et al., 'Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.', Immunity, 56 1098-1114.e10 (2023) [C1]
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Nova |
2023 |
Bernstein IR, Nixon B, Lyons JM, Damyanova KB, De Oliveira CS, Mabotuwana NS, et al., 'The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions', iScience, 26 108424-108424 (2023) [C1]
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Nova |
2023 |
Gilbert B, Kaiko G, Smith S, Wark P, 'A systematic review of the colorectal microbiome in adult cystic fibrosis patients.', Colorectal Dis, 25 843-852 (2023) [C1]
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Nova |
2022 |
Jamaluddin MFB, Ghosh A, Ingle A, Mohammed R, Ali A, Bahrami M, et al., 'Bovine and human endometrium-derived hydrogels support organoid culture from healthy and cancerous tissues', Proceedings of the National Academy of Sciences, 119 (2022) [C1]
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Nova |
2022 |
Dowling LR, Strazzari MR, Keely S, Kaiko GE, 'Enteric nervous system and intestinal epithelial regulation of the gut-brain axis', Journal of Allergy and Clinical Immunology, 150 513-522 (2022) [C1]
The gut-brain axis describes a bidirectional interplay within the enteric environment between the intestinal epithelium, the mucosal immune system, and the microbiota with the ent... [more]
The gut-brain axis describes a bidirectional interplay within the enteric environment between the intestinal epithelium, the mucosal immune system, and the microbiota with the enteric nervous system. This interplay provides a link between exogenous environmental stimuli such as nutrient sensing, and nervous system function, as well as a mechanism of feedback from cortical and sensory centers of the brain to enteric activities. The intestinal epithelium is one of the human body's largest sources of hormones and neurotransmitters, which have critical effects on neuronal function. The influence of the gut microbiota on these processes appears to be profound; yet to date, it has been insufficiently explored. Disruption of the intestinal microbiota is linked not only to diseases in the gut but also to brain symptomatology, including neurodegenerative and behavioral disorders (Parkinson disease, Alzheimer disease, autism, and anxiety and/or depression). In this review we discuss the cellular wiring of the gut-brain axis, with a particular focus on the epithelial and neuronal interaction, the evidence that has led to our current understanding of the intestinal role in neurologic function, and future directions of research to unravel this important interaction in both health and allergic disease.
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Nova |
2022 |
Bruce JK, Burns GL, Sinn Soh W, Nair PM, Sherwin S, Fan KN, et al., 'Defects in NLRP6, autophagy and goblet cell homeostasis are associated with reduced duodenal CRH receptor 2 expression in patients with functional dyspepsia', Brain, Behavior, and Immunity, 101 335-345 (2022) [C1]
Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identif... [more]
Functional dyspepsia (FD) affects up to 15% of the population and is characterised by recurring upper gastrointestinal (GI) symptoms occurring in the absence of clinically identifiable pathology. Psychological stress is a key factor associated with the onset of FD and locally acting hypothalamic¿pituitary¿adrenal (HPA) axis hormones have been implicated in GI motility and barrier dysfunction. Recent pre-clinical work has identified mechanistic pathways linking corticotropin-releasing hormone (CRH) with the innate epithelial immune protein NLRP6, an inflammasome that has been shown to regulate GI mucus secretion. We recruited twelve FD patients and twelve healthy individuals to examine whether dysregulation of hypothalamic-pituitary adrenal (HPA) axis hormones and altered NLRP6 pathways were evident in the duodenal mucosa. Protein expression was assessed by immunoblot and immunohistochemistry in D2 duodenal biopsies. Plasma HPA axis hormones were assayed by ELISA and enteroid and colorectal cancer cell line cultures were used to verify function. FD patients exhibited reduced duodenal CRH-receptor 2, compared to non-GI disease controls, indicating a dysregulation of duodenal HPA signalling. The loss of CRH-receptor 2 correlated with reduced NLRP6 expression and autophagy function, processes critical for maintaining goblet cell homeostasis. In accordance, duodenal goblet cell numbers and mucin exocytosis was reduced in FD patients compared to controls. In vitro studies demonstrated that CRH could reduce NLRP6 in duodenal spheroids and promote mucus secretion in the HT29-MTX-E12 cell line. In conclusion, FD patients exhibit defects in the NLRP6-autophagy axis with decreased goblet cell function that may drive symptoms of disease. These features correlated with loss of CRH receptor 2 and may be driven by dysregulation of HPA signalling in the duodenum of FD patients.
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Nova |
2021 |
Bekkers M, Stojkovic B, Kaiko GE, 'Mining the Microbiome and Microbiota-Derived Molecules in Inflammatory Bowel Disease', INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (2021) [C1]
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Nova |
2021 |
Wark PAB, Pathinayake PS, Kaiko G, Nichol K, Ali A, Chen L, et al., 'ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma', Respirology, 26 442-451 (2021) [C1]
Background and objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine protea... [more]
Background and objective: COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD. Methods: We obtained lower AEC from 145 people from two independent cohorts, aged 2¿89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC. Results: Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients. Conclusion: Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.
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Nova |
2021 |
Barnes JL, Plank MW, Asquith K, Maltby S, Sabino LR, Kaiko GE, et al., 'T-helper 22 cells develop as a distinct lineage from Th17 cells during bacterial infection and phenotypic stability is regulated by T-bet', MUCOSAL IMMUNOLOGY, 14 1077-1087 (2021) [C1]
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Nova |
2020 |
Sokulsky LA, Garcia-Netto K, Nguyen TH, Girkin JLN, Collison A, Mattes J, et al., 'A critical role for the CXCL3/CXCL5/CXCR2 neutrophilic chemotactic axis in the regulation of type 2 responses in a model of rhinoviral-induced asthma exacerbation', Journal of Immunology, 205 2468-2478 (2020) [C1]
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Nova |
2020 |
Sokulsky LA, Goggins B, Sherwin S, Eyers F, Kaiko GE, Board PG, et al., 'GSTO1-1 is an upstream suppressor of M2 macrophage skewing and HIF-1a-induced eosinophilic airway inflammation', CLINICAL AND EXPERIMENTAL ALLERGY, 50 609-624 (2020) [C1]
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Nova |
2020 |
Ali A, Tan H, Kaiko GE, 'Role of the Intestinal Epithelium and Its Interaction With the Microbiota in Food Allergy', FRONTIERS IN IMMUNOLOGY, 11 (2020) [C1]
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Nova |
2019 |
Starkey MR, Plank MW, Casolari P, Papi A, Pavlidis S, Guo Y, et al., 'IL-22 and its receptors are increased in human and experimental COPD and contribute to pathogenesis', EUROPEAN RESPIRATORY JOURNAL, 54 (2019) [C1]
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Nova |
2019 |
Kaiko GE, Chen F, Lai C-W, Chiang I-L, Perrigoue J, Stojmirovic A, et al., 'PAI-1 augments mucosal damage in colitis', SCIENCE TRANSLATIONAL MEDICINE, 11 (2019) [C1]
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Nova |
2018 |
Liu TC, Kern JT, VanDussen KL, Xiong S, Kaiko GE, Wilen CB, et al., 'Interaction between smoking and ATG16L1
It is suggested that subtyping of complex inflammatory diseases can be based on genetic susceptibility and relevant environmental exposure (G+E). We propose that using matched cel... [more]
It is suggested that subtyping of complex inflammatory diseases can be based on genetic susceptibility and relevant environmental exposure (G+E). We propose that using matched cellular phenotypes in human subjects and corresponding preclinical models with the same G+E combinations is useful to this end. As an example, defective Paneth cells can subtype Crohn's disease (CD) subjects; Paneth cell defects have been linked to multiple CD susceptibility genes and are associated with poor outcome. We hypothesized that CD susceptibility genes interact with cigarette smoking, a major CD environmental risk factor, to trigger Paneth cell defects. We found that both CD subjects and mice with ATG16L1T300A (T300A; a prevalent CD susceptibility allele) developed Paneth cell defects triggered by tobacco smoke. Transcriptional analysis of full-thickness ileum and Paneth cell-enriched crypt base cells showed the T300A-smoking combination altered distinct pathways, including proapoptosis, metabolic dysregulation, and selective downregulation of the PPAR¿ pathway. Pharmacologic intervention by either apoptosis inhibitor or PPAR¿ agonist rosiglitazone prevented smoking-induced crypt apoptosis and Paneth cell defects in T300A mice and mice with conditional Paneth cell-specific knockout of Atg16l1. This study demonstrates how explicit G+E can drive disease-relevant phenotype and provides rational strategies for identifying actionable targets.
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2018 |
Ryu SH, Kaiko GE, Stappenbeck TS, 'Cellular differentiation: Potential insight into butyrate paradox?', Molecular and Cellular Oncology, 5 (2018) [C1]
We recently demonstrated that cellular responses to butyrate depend on the differentiation status of the colonic epithelium. Here, we apply the implications of these findings to c... [more]
We recently demonstrated that cellular responses to butyrate depend on the differentiation status of the colonic epithelium. Here, we apply the implications of these findings to cancer biology and discuss discrepancies in the effects of butyrate on cancer progression.
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2018 |
Kaiko GE, Wark PAB, 'Developments in cystic fibrosis personalised epithelial assays: Science and patient perspectives', JOURNAL OF CYSTIC FIBROSIS, 17 289-291 (2018)
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2017 |
Steed AL, Christophi GP, Kaiko GE, Sun L, Goodwin VM, Jain U, et al., 'The microbial metabolite desaminotyrosine protects from influenza through type I interferon', Science, 357 498-502 (2017) [C1]
The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects thr... [more]
The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.
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2017 |
Plank MW, Kaiko GE, Maltby S, Weaver J, Tay HL, Shen W, et al., 'Th22 Cells Form a Distinct Th Lineage from Th17 Cells In Vitro with Unique Transcriptional Properties and Tbet-Dependent Th1 Plasticity.', JOURNAL OF IMMUNOLOGY, 198 2182-2190 (2017) [C1]
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Nova |
2017 |
Foster PS, Maltby S, Rosenberg HF, Tay HL, Hogan SP, Collison AM, et al., 'Modeling T
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Nova |
2016 |
Kaiko GE, Ryu SH, Koues OI, Collins PL, Solnica-Krezel L, Pearce EJ, et al., 'The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites', Cell, 165 1708-1720 (2016) [C1]
In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial... [more]
In the mammalian intestine, crypts of Leiberkühn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial metabolite compounds that potentially modulate stem/progenitor cell activity. Unbiased screening identified butyrate, a prominent bacterial metabolite, as a potent inhibitor of intestinal stem/progenitor proliferation at physiologic concentrations. During homeostasis, differentiated colonocytes metabolized butyrate likely preventing it from reaching proliferating epithelial stem/progenitor cells within the crypt. Exposure of stem/progenitor cells in vivo to butyrate through either mucosal injury or application to a naturally crypt-less host organism led to inhibition of proliferation and delayed wound repair. The mechanism of butyrate action depended on the transcription factor Foxo3. Our findings indicate that mammalian crypt architecture protects stem/progenitor cell proliferation in part through a metabolic barrier formed by differentiated colonocytes that consume butyrate and stimulate future studies on the interplay of host anatomy and microbiome metabolism.
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2016 |
Kaiko GE, Ryu SH, Koues OI, Collins PL, Solnica-Krezel L, Pearce EJ, et al., 'The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites (vol 165, pg 1708, 2016)', CELL, 167 1137-1137 (2016)
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2016 |
Brody SL, Kaiko GE, 'Harnessing TGF-ß and BMP signaling for expansion of p63-positive epithelial stem cells.', Stem cell investigation, 3 82 (2016)
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2015 |
Hickey CA, Kuhn KA, Donermeyer DL, Porter NT, Jin C, Cameron EA, et al., 'Colitogenic Bacteroides thetaiotaomicron antigens access host immune cells in a sulfatase-dependent manner via outer membrane vesicles', Cell Host and Microbe, 17 672-680 (2015) [C1]
Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanism is the method by which intestinal microbes or their antigens ... [more]
Microbes interact with the host immune system via several potential mechanisms. One essential step for each mechanism is the method by which intestinal microbes or their antigens access specific host immune cells. Using genetically susceptible mice (dnKO) that develop spontaneous, fulminant colitis, triggered by Bacteroides thetaiotaomicron (B. theta), we investigated the mechanism of intestinal microbial access under conditions that stimulate colonic inflammation. B. theta antigens localized to host immune cells through outer membrane vesicles (OMVs) that harbor bacterial sulfatase activity. We deleted the anaerobic sulfatase maturating enzyme (anSME) from B. theta, which is required for post-translational activation of all B. theta sulfatase enzymes. This bacterial mutant strain did not stimulate colitis in dnKO mice. Lastly, access of B. theta OMVs to host immune cells was sulfatase dependent. These data demonstrate that bacterial OMVs and associated enzymes promote inflammatory immune stimulation in genetically susceptible hosts.
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2015 |
Tay HL, Kaiko GE, Plank M, Li J, Maltby S, Essilfie A-T, et al., 'Correction: Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung.', PLoS pathogens, 11 e1004956 (2015) [O1]
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2015 |
Tay HL, Kaiko GE, Plank M, Li JJ, Maltby S, Essilfie AT, et al., 'Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung', PLoS Pathogens, 11 (2015) [C1]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibio... [more]
Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases.
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Nova |
2014 |
Kaiko GE, Stappenbeck TS, 'Host-microbe interactions shaping the gastrointestinal environment', Trends in Immunology, 35 538-548 (2014)
Tremendous advances have been made in mapping the complexity of the human gut microbiota in both health and disease states. These analyses have revealed that, rather than a conste... [more]
Tremendous advances have been made in mapping the complexity of the human gut microbiota in both health and disease states. These analyses have revealed that, rather than a constellation of individual species, a healthy microbiota comprises an interdependent network of microbes. The microbial and host interactions that shape both this network and the gastrointestinal environment are areas of intense investigation. Here we review emerg-ing concepts of how microbial metabolic processes con-trol commensal composition, invading pathogens, immune activation, and intestinal barrier function. We posit that all of these factors are critical for the mainte-nance of homeostasis and avoidance of overt inflamma- tory disease. A greater understanding of the underlying mechanisms will shed light on the pathogenesis of many diseases and guide new therapeutic interventions.
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2013 |
Kaiko G, Loh Z, Spann K, Lynch J, Lalwani A, Davidson S, et al., 'TLR7 gene deficiency and early-life pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice', EUROPEAN RESPIRATORY JOURNAL, 42 (2013) |
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2013 |
Kaiko GE, Loh Z, Spann K, Lynch JP, Lalwani A, Zheng Z, et al., 'Toll-like receptor 7 gene deficiency and early-life
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Nova |
2013 |
Foster PS, Plank MW, Collison AM, Tay HL, Kaiko GE, Li J, et al., 'The emerging role of microRNAs in regulating immune and inflammatory responses in the lung', Immunological Reviews, 253 198-215 (2013) [C1]
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Nova |
2013 |
Hansbro PM, Scott GV, Essilfie A-T, Kim RY, Starkey MR, Nguyen D, et al., 'Th2 cytokine antagonists: Potential treatments for severe asthma', Expert Opinion on Investigational Drugs, 22 49-69 (2013) [C1]
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Nova |
2011 |
Kaiko GE, Foster PS, 'New insights into the generation of Th2 immunity and potential therapeutic targets for the treatment of asthma', Current Opinion in Allergy and Clinical Immunology, 11 39-45 (2011) [C1]
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Nova |
2011 |
Asquith KL, Horvat JC, Kaiko GE, Carey AJ, Beagley KW, Hansbro PM, Foster PS, 'Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts', PLoS Pathogens, 7 (2011) [C1]
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Nova |
2011 |
Hansbro PM, Kaiko GE, Foster PS, 'Cytokine/anti-cytokine therapy - Novel treatments for asthma?', British Journal of Pharmacology, 163 81-95 (2011) [C2]
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Nova |
2011 |
Davidson SK, Kaiko GE, Loh Z, Lalwani A, Zhang V, Spann K, et al., 'Plasmacytoid Dendritic Cells promote host defense against Acute Pneumovirus infection via the TLR7-MyD88-Dependent signaling pathway', Journal of Immunology, 186 5938-5948 (2011) [C1]
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Nova |
2011 |
Kumar RK, Siegle JS, Kaiko GE, Herbert C, Mattes JE, Foster PS, 'Responses of airway epithelium to environmental injury: role in the induction phase of childhood asthma.', Journal of allergy, 2011 257017 (2011)
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2010 |
Kaiko GE, Phipps S, Angkasekwinai P, Dong C, Foster PS, 'NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL-25', Journal of Immunology, 185 4681-4690 (2010) [C1]
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Nova |
2009 |
Phipps S, Lam CE, Kaiko GE, Foo A, Collison AM, Mattes J, et al., 'Toll/IL-1 signaling is critical for house dust mite-specific Th1 and Th2 responses', American Journal of Respiratory and Critical Care Medicine, 179 883-893 (2009) [C1]
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Nova |
2008 |
Kaiko GE, Horvat JC, Beagley KW, Hansbro PM, 'Immunological decision-making: How does the immune system decide to mount a helper T-cell response?', Immunology, 123 326-338 (2008) [C1]
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Nova |
2008 |
Kaiko GE, Phipps S, Hickey DK, Lam CE, Hansbro PM, Foster PS, Beagley KW, 'Chlamydia muridarum infection subverts dendritic cell function to promote Th2 immunity and airways hyperreactivity', Journal of Immunology, 180 2225-2232 (2008) [C1]
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Nova |
2007 |
Horvat JC, Beagley KW, Wade MA, Preston JA, Hansbro NG, Hickey DK, et al., 'Neonatal chlamydial infection induces mixed T-cell responses that drive allergic airway disease', American Journal of Respiratory and Critical Care Medicine, 176 556-564 (2007) [C1]
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Nova |