A5015651654- Immune cells in cancer
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Bone Metabolism and Diseases
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Digestive system and related health
- Acute Myeloid Leukemia Research
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Probiotics and Fermented Foods
- IL-33, ST2, and ILC Pathways
- Reproductive System and Pregnancy
- Prion Diseases and Protein Misfolding
- Extracellular vesicles in disease
- Celiac Disease Research and Management
- interferon and immune responses
- Gut microbiota and health
- Eosinophilic Esophagitis
- RNA regulation and disease
Translational Research Institute
2020-2025
The University of Queensland
2019-2025
Mater Research
2019-2025
Wesley Research Institute
2023
University of Edinburgh
2014-2018
Roslin Institute
2014-2018
École Nationale Vétérinaire d'Alfort
2014
Département Santé Animale
2014
Wageningen University & Research
2014
VIB-UGent Center for Inflammation Research
2014
Abstract Colony-stimulating factor 1 (CSF1) controls the growth and differentiation of macrophages.CSF1R signaling has been implicated in maintenance intestinal stem cell niche Paneth cells, but evidence expression CSF1R within crypt is equivocal. Here we show that CSF1R-dependent macrophages influence epithelial homeostasis. In lamina propria mRNA restricted to which are intimately associated with epithelium, undetectable cells. Macrophage ablation following blockade affects leads a...
Abstract We investigated the role of CSF1R signaling in adult mice using prolonged treatment with anti-CSF1R antibody. Mutation CSF1 gene op/op mouse produces numerous developmental abnormalities. has an even more penetrant phenotype, including perinatal lethality, because existence a second ligand, IL-34. These effects on development provide limited insight into functions homeostasis. The carcass weight and several organs (spleen, kidney, liver) were reduced treated mice, but overall body...
We have produced an Fc conjugate of colony-stimulating factor (CSF) 1 with improved circulating half-life. CSF1-Fc retained its macrophage growth-promoting activity, and did not induce proinflammatory cytokines in vitro. Treatment produce adverse effects mice or pigs. The impact was examined using the Csf1r-enhanced green fluorescent protein (EGFP) reporter gene MacGreen mice. Administration to drove extensive infiltration all tissues by Csf1r-EGFP positive macrophages. main consequence...
Abstract The proliferation, differentiation, and survival of cells the mononuclear phagocyte system (MPS; progenitors, monocytes, macrophages, classical dendritic cells) are controlled by signals from M-CSF receptor (CSF1R). Cells MPS lineage have been identified using numerous surface markers transgenic reporters, but none is both universal restricted. In this article, we report development characterization a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with C...
Homozygous mutation of the Csf1r locus ( Csf1rko ) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis mechanisms underlying phenotypic impacts mutation, we bred a rat allele inbred dark agouti (DA) genetic background -mApple reporter transgene. The led almost complete loss embryonic macrophages ablation most adult tissue macrophage populations. We extended previous phenotype early development reveal on musculoskeletal proliferation...
Cattle are an economically important domestic animal species. In vitro 2D cultures of intestinal epithelial cells or cell lines have been widely used to study function and host–pathogen interactions in the bovine intestine. However, these lack cellular diversity encountered epithelium, physiological relevance monocultures transformed is uncertain. Little also known factors that influence differentiation homeostasis few cell-specific markers can distinguish different lineages reported. Here...
The MacBlue transgenic mouse uses the Csf1r promoter and first intron to drive expression of gal4-VP16, which in turn drives a cointegrated gal4-responsive UAS-ECFP cassette. region used contains deletion 150 bp conserved covering trophoblast osteoclast-specific transcription start sites. In this study, we examined transgene embryos adult mice. embryos, ECFP was expressed large majority macrophages derived from yolk sac, as liver became major site monocytopoiesis. adults, detected at high...
Many natural prion diseases of humans and animals are considered to be acquired through oral consumption contaminated food or pasture. Determining the route by which prions establish host infection will identify important factors that influence disease susceptibility intervention strategies can developed. After exposure, early accumulation replication within small intestinal Peyer's patches is essential for efficient spread brain. To replicate patches, must first cross gut epithelium. M...
Abstract Macrophages are present in large numbers every tissue the body where they play critical roles development and homeostasis. They exhibit remarkable phenotypic functional diversity, underpinning their adaptation to specialized each niche. CSF1, signaling through CSF1 receptor, which is restricted monocyte-macrophage lineage cells adults, a growth factor controlling macrophage proliferation, differentiation, many aspects of mature function. We have generated reporter rat, utilizing...
ABSTRACT Amino acid substitutions in the kinase domain of human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy axonal spheroids and pigmented glia (ALSP). To model disease, we created a disease-associated mutation (pGlu631Lys; E631K) mouse Csf1r locus. Homozygous (Csf1rE631K/E631K) phenocopied knockout, prenatal mortality or severe postnatal growth retardation hydrocephalus. Heterozygous delayed expansion tissue macrophage populations most organs. Bone...
Adaptation to existence outside the womb is a key event in life of mammal. The absence macrophages rats with homozygous mutation colony-stimulating factor 1 receptor ( Csf1r) gene Csf1rko ) severely compromises pre-weaning somatic growth and maturation organ function. Transfer wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development long-term survival. To dissect phenotype function postnatal development, we generated transcriptomic...
Macrophage and osteoclast proliferation, differentiation survival are regulated by colony-stimulating factor 1 receptor (CSF1R) signaling. Osteopetrosis associated with Csf1 Csf1r mutations has been attributed to the loss of osteoclasts deficiency in bone resorption. Here, we demonstrate that homozygous mutation rat leads delayed postnatal skeletal ossification substantial osteal macrophages addition osteoclasts. Osteosclerosis site-specific abnormalities were reversed intraperitoneal...
Abstract Background Prior chemotherapy and/or underlying morbidity commonly leads to poor mobilisation of hematopoietic stem cells (HSC) for transplantation in cancer patients. Increasing the number available HSC prior is a potential strategy overcome this deficiency. Resident bone marrow (BM) macrophages are essential maintenance niches that support and enable engraftment transplant recipients. Here we examined donor treatment with modified recombinant colony-stimulating factor 1 (CSF1)...
Abstract Homozygous null mutation of the Csf1r gene ( Csf1rko ) in rats leads to loss most tissue macrophage populations and pleiotropic impacts on postnatal growth organ maturation, leading early mortality. The phenotype can be reversed by intraperitoneal transfer WT BM cells (BMT) at weaning. Here, we used a ‐mApple transgenic reporter track fate donor‐derived cells. Following BMT into recipients, mApple +ve restored IBA1 + every tissue. However, monocytes, neutrophils, B BM, blood,...
Abstract Adaptation to existence outside the womb is a key event in life of mammal. The absence macrophages rats with homozygous mutation Csf1r gene ( Csf1rko ) severely compromises pre-weaning somatic growth and maturation organ function. Transfer wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development long-term survival. To dissect phenotype function postnatal development, we generated transcriptomic profiles all major organs...
M cells reside within the follicle-associated epithelium (FAE) overlying gut-associated lymphoid tissues. These unique phagocytic epithelial enable mucosal immune system to sample antigens lumen of intestine. The differentiation from uncommitted precursors in FAE is dependent on production receptor activator nuclear factor-κB ligand (RANKL) by subepithelial stromal cells. ligation a variety cell surface receptors activates (NF-κB) family transcription factors which in-turn induce multiple...
Summary Mouse hematopoietic tissues contain abundant and heterogeneous populations of tissue-resident macrophages attributed trophic functions in control immunity, hematopoiesis bone homeostasis. A systematic strategy to characterise macrophage subsets mouse marrow (BM), spleen lymph node, unexpectedly revealed surface marker staining typically emanated from membrane-bound subcellular remnants associated with unrelated cell types. Remnant-restricted macrophage-specific membrane markers,...
Abstract The proliferation, differentiation and survival of cells the mononuclear phagocyte system (MPS, progenitors, monocytes, macrophages classical dendritic cells) is controlled by signals from macrophage colony-stimulating factor receptor (CSF1R). Cells MPS lineage have been identified using numerous surface markers transgenic reporters but none both universal lineage-restricted. Here we report development characterization a novel CSF1R reporter mouse. A Fusion Red (FRed) cassette was...