A5050863147- Immune cells in cancer
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Osteoarthritis Treatment and Mechanisms
- Signaling Pathways in Disease
- Rheumatoid Arthritis Research and Therapies
- Inflammatory mediators and NSAID effects
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Cellular transport and secretion
- TGF-β signaling in diseases
- Reproductive System and Pregnancy
- Inflammasome and immune disorders
- Bacterial Genetics and Biotechnology
- Oral microbiology and periodontitis research
- NF-κB Signaling Pathways
- Psoriasis: Treatment and Pathogenesis
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Toxin Mechanisms and Immunotoxins
- Heat shock proteins research
- interferon and immune responses
The Royal Melbourne Hospital
2016-2025
The University of Melbourne
2016-2025
Peter Doherty Institute
2023
McMaster University
2020
Australian Institute for Musculoskeletal Science
2019
National Centre for Biological Sciences
2019
Burnet Institute
2010
Abstract GM-CSF and M-CSF (CSF-1) induce different phenotypic changes in macrophage lineage populations. The nature, extent, generality of these differences were assessed by comparing the responses to CSFs, either alone or combination, various human murine between respective global gene expression profiles macrophages, derived from monocytes M-CSF, compared with for bone marrow cells each CSF. Only 17% genes regulated differently CSFs common across species. Whether a particular change...
Abstract Tumor-associated macrophages (TAMs), one of the most abundant immune components in gastric cancer (GC), are difficult to characterize due their heterogeneity. Multiple approaches have been used elucidate issue, however, tissue-destructive nature these methods, spatial distribution TAMs situ remains unclear. Here we probe relationship between tumor context and TAM heterogeneity by multiplex immunohistochemistry 56 human GC cases. Using distinct expression marker profiles on TAMs,...
Porphyromonas gingivalis is one of the bacterial species most closely associated with periodontitis and can shed large numbers outer membrane vesicles (OMVs), which are increasingly thought to play a significant role in virulence pathogenicity. Macrophages amongst first immune cells respond bacteria their products, so we sought directly compare response macrophages P. or its purified OMVs. stimulated OMVs produced amounts TNFα, IL-12p70, IL-6, IL-10, IFNβ, nitric oxide compared infected...
Data from preclinical and clinical studies have demonstrated that granulocyte macrophage colony-stimulating factor (GM-CSF) can function as a key proinflammatory cytokine. However, therapies directly target GM-CSF could lead to undesirable side effects, creating need delineate downstream pathways mediators. In this work, we provide evidence drives CCL17 production by acting through an IFN regulatory 4-dependent (IRF4-dependent) pathway in human monocytes, murine macrophages, mice vivo....
Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number inflammatory diseases and osteoarthritis (OA). We identified previously new GM-CSF→Jmjd3→interferon regulatory 4 (IRF4)→chemokine (c-c motif) ligand 17 (CCL17) pathway, which is important for development arthritis pain disease. Tumour necrosis (TNF) can also be linked with this pathway. Here we investigated involvement pathway OA disease using GM-CSF-dependent collagenase-induced...
Macrophage activation in response to LPS is coupled profound metabolic changes, typified by accumulation of the TCA cycle intermediates citrate, itaconate, and succinate. We have identified that endogenous type I IFN controls cellular citrate/α-ketoglutarate ratio inhibits expression activity isocitrate dehydrogenase (IDH); and, via 13C-labeling studies, demonstrated autocrine carbon flow through IDH LPS-activated macrophages. also found IFN–driven IL-10 contributes inhibition itaconate...
Metabolic adaptations can directly influence the scope and scale of macrophage activation polarization. Here we explore impact type I interferon (IFNβ) on metabolism its broader cytokine signaling pathways. We find that IFNβ simultaneously increased expression immune-responsive gene 1 itaconate production while inhibiting isocitrate dehydrogenase activity restricting α-ketoglutarate accumulation. also flux glutamine-derived carbon into tricarboxylic acid cycle to boost succinate levels....
Abstract Macrophages are heterogeneous innate immune cells that functionally shaped by their surrounding microenvironment. Diverse macrophage populations have multifaceted differences related to morphology, metabolism, expressed markers, and functions, where the identification of different phenotypes is an utmost importance in modelling response. While markers most used signature classify phenotypes, multiple reports indicate morphology autofluorescence also valuable clues can be process. In...
Abstract Glucocorticoids (GCs) are potent anti-inflammatory drugs whose mode of action is complex and still debatable. One likely cellular target GCs monocytes/macrophages. The role in monocyte survival also debated. Although both granulocyte macrophage-colony stimulating factor (GM-CSF) macrophage-CSF (M-CSF) important regulators macrophage lineage functions including their survival, the former often associated with proinflammatory while latter homeostasis. We report here that GC,...
Abstract Urokinase plasminogen activator (uPA) and its receptor (uPAR) coordinate a plasmin-mediated proteolytic cascade that has been implicated in cell adhesion, motility, matrix breakdown, for example, during inflammation. As part of their function inflammatory responses, macrophages move through tissues encounter both two-dimensional (2D) surfaces more complex three-dimensional (3D) interstitial matrices. Based on approaches employing uPA gene–deficient macrophages, supplementation,...
Transforming growth factor-β (TGF-β) is a pleiotropic cytokine essential for multiple biological processes, including the regulation of inflammatory and immune responses. One important functions TGF-β suppression proinflammatory interleukin-12 (IL-12), which crucial mounting an anti-tumorigenic response. Although IL-12p40 subunit (encoded by IL-12B gene) IL-12 has been extensively investigated, knowledge IL-12p35 IL-12A relatively limited. This study investigates molecular TGF-β-activated...
We previously reported that CCL17 gene-deficient mice are protected from developing pain-like behaviour and exhibit less disease in destabilization of medial meniscus (DMM)-induced OA, as well high-fat diet (HFD)-exacerbated DMM-induced OA. Here, we explored if therapeutic neutralization CCL17, using increasing doses a neutralizing monoclonal antibody (mAb), would lead to dose-dependent benefit these two models. OA was initiated male either fed with control (7% fat) or 8 weeks 60% HFD,...
IFN regulatory factors (IRFs) help to shape the immune response pathogens by imparting signaling specificity individual TLRs. We recently demonstrated that IRF6 provides TLR2 in oral epithelial cells. plays an important role eliciting inflammation Porphyromonas gingivalis, a keystone pathogen periodontitis. Therefore, we investigated for mediating inflammatory cytokine of cells P. gingivalis. expression was strongly upregulated when human were challenged with Moreover, gene silencing and...
TNF and granulocyte macrophage-colony stimulating factor (GM-CSF) have proinflammatory activity both contribute, for example, to rheumatoid arthritis pathogenesis. We previously identified a new GM-CSF→JMJD3 demethylase→interferon regulatory 4 (IRF4)→CCL17 pathway that is active in monocytes/macrophages vitro important inflammatory pain, as well arthritic pain disease. Here we provide evidence nexus between this pathway, GM-CSF interdependency. report the initiation of zymosan-induced...
Abstract G-CSF or CSF-3, originally defined as a regulator of granulocyte lineage development via its cell surface receptor (G-CSFR), can play role in inflammation, and hence many pathologies, due to effects on mature populations. Given this, because pain is an extremely important arthritis symptom, the efficacy anti–G-CSFR mAb for arthritic disease was compared with that neutrophil-depleting mAb, anti-Ly6G, both adaptive innate immune-mediated murine models. Pain were ameliorated Ag-induced...
Abstract Studies have demonstrated the importance of a GM-CSF→IFN regulatory factor 4 (IRF4)→CCL17 pathway, first identified in monocytes/macrophages, for arthritic pain and disease development. In this study, we further investigated involvement new pathway shaping inflammatory response using zymosan-induced peritonitis (ZIP) model. ZIP (8 mg zymosan, i.p., day 0) was induced C57BL/6 wild-type (WT), GM-CSF−/−, Irf4−/−, Ccl17E/E mice. comparison with WT mice, GM-CSF−/− Irf4−/− mice had...