Targeted deletion of GM-CSF from immune cell populations and the effect on inflammatory arthritis
Project type
PhD
| Supervisor(s) | Division | |
| (Primary) | Inflammation | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Cancer and Haematology | .(JavaScript must be enabled to view this email address) |
Details of project
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth and differentiation factor for haemopoietic progenitor cells, but can also function as pro-inflammatory mediator in a range of pathological conditions, like rheumatoid arthritis (RA). GM‑CSF can be produced by a wide variety of cell types, including T cells, macrophages, endothelial cells and fibroblasts. GM-CSF antagonism has a profound therapeutic effect in experimental models of RA, and the GM-CSF knockout mouse is protected from experimental inflammatory arthritis.
The project involves use of the cre-lox system to generate conditional knock-out mouse models. A GM-CSF transgene flanked by LoxP sites is currently being prepared. This transgene will be crossed with cre-expressing mouse models to knock out GM-CSF specifically in the desired cell type.
Development of the haemopoietic and lymphoid systems will be analysed by automated cell counting, FACS, histology and immunohistochemistry. Multiple models of inflammatory arthritis will be used to study the effect of deleting GM-CSF from specific cell types during inflammation.
Research interests
Inflammatory diseases, including rheumatoid arthritis and gout, are the main research focus of the Reid Laboratory. Our research centres around the investigation of cellular responses to inflammation and the cytokines involved in inflammatory pathways.
A large portion of our research is conducted using murine models of inflammatory diseases. However, we have strong ties with the Royal Melbourne Hospital and our ultimate aim is to translate our research into the clinic.
Selected publications
- Lawlor KE, Smith SD, van Nieuwenhuijze A, Huang DC, Wicks IP. Evaluation of the Bcl-2 family antagonist ABT-737 in collagen-induced arthritis. J Leukoc Biol. 2011 Jun 30 (in press). PMID: 21719460
- Zhan Y, Carrington EM, van Nieuwenhuijze A, Bedoui S, Seah S, Xu Y, Wang N, Mintern JD, Villadangos JA, Wicks IP, Lew AM. GM-CSF increases cross-presentation and CD103 expression by mouse CD8(+) spleen dendritic cells. Eur J Immunol. 2011 Jun 10 (in press). PMID: 21660938
- Campbell IK, van Nieuwenhuijze A, Segura E, O'Donnell K, Coghill E, Hommel M, Gerondakis S, Villadangos JA, Wicks IP. Differentiation of inflammatory dendritic cells is mediated by NF-κB1-dependent GM-CSF production in CD4 T cells. J Immunol. 2011 May 1;186(9):5468-77. PMID: 21421852
Research theme
Chronic inflammatory diseases
Scientific discipline
- Immunology
- Innate Immunity
Keywords
arthritis, mouse models, cytokines, transgenic