w.sewell@garvan.unsw.edu.au

Garvan Institute of Medical Research. Ph. 9295 8434

Allergic diseases and cytokines

Allergic asthma and other allergic diseases are common conditions and a major burden to the community. Cytokines produced by CD4+ T cells are prominent in the affected tissues in these diseases where they are important mediators of inflammation.  The best characterized of these are the TH2 cytokines IL-4, IL-5 and IL-13.  GM-CSF is a related cytokine that has many inflammatory effects on a variety of cells including dendritic cells, macrophages, neutrophils, eosinophils and non-haemopoietic cells.  GM-CSF can be produced by TH1 cells and non-T cells as well as by TH2 cells.

Project 1: Role of GM-CSF in allergic inflammation (in collaboration with Dr Michael Rolph and Prof Charles Mackay)
Availability for one student

We have observed that in a model of allergic asthma, inflammation is markedly reduced in GM-CSF knock-out mice.  In the knock-out mice, infiltration of eosinophils into the airways is particularly reduced, even though these cells are present around the blood vessels in the lung tissue.  The knock-out mice also have defective production of the TH2 cytokine IL-5.  The project will test the hypothesis that there is defective antigen presentation in the GM-CSF knockout mice, leading to defective T cell responses including reduced IL-5 production.  The project aims to measure the capacity of antigen-presenting cells and T cells from GM-CSF knockout mice to generate immune responses.  Experimental techniques will include ELISA, real time PCR, flow cytometry and analysis of gene array data.  

Selected general references

• Ritz SA, Stampfli MR, Davies DE, Holgate ST, Jordana M. On the generation of allergic airway diseases: from GM-CSF to Kyoto. Trends Immunol 2002;23(8):396-402.

• Su YC, Rolph MS, Cooley MA, Sewell WA.  Cyclophosphamide Augments Inflammation by Reducing Immunosuppression in a Mouse Model of Allergic Airway Disease. J Allerg Clin Immunol 2006:117: 635-641.