Monday, 5 December 2011
Poster Hall (Cancún Center)
Jaisubash Jayakumar
,
Division of Immunology, International Centre for Genetic Engineering and Biotechnology, Institue of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Natalie Nieuwenhuizen
,
Division of Immunology, International Centre for Genetic Engineering and Biotechnology, Institue of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Frank Kirstein
,
Division of Immunology, International Centre for Genetic Engineering and Biotechnology, Institue of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Babele Emedi
,
Division of Immunology, International Centre for Genetic Engineering and Biotechnology, Institue of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Frank Brombacher
,
Division of Immunology, International Centre for Genetic Engineering and Biotechnology, Institue of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Background: Asthma is a chronic inflammatory disease of the lungs affecting approximately 300 million people worldwide. Mouse models mimicking features of asthma such as airway hyperreactivity (AHR) and inflammation have demonstrated an important role for the IL-4Rα,IL-4 and IL-13 in the pathology of this disease. However, the effects of IL-4 and IL-13 signaling through specific cell types in asthma remain to be elucidated. The aim of our study is to investigate the role of IL4Rα expression on CD4
+ T cells in ovalbumin (OVA)-induced allergic airway disease.
Methods: Mice with cell specific impairment of IL-4Rα on CD4+ T cells (LckcreIL-4Rα-/lox), IL-4Rα-/lox littermate controls and IL-4Rα-/- mice were sensitized with OVA adsorbed to alum and challenged intranasally with OVA. At day 60, AHR was measured by Flexivent in response to increasing doses of methacholine, and samples were taken for analysis.
Results: Airway resistance and elastance were significantly increased in OVA-challenged IL-4Rα-/lox mice compared to PBS controls. Both global IL-4Rα-/- and LckcreIL-4Rα-/lox mice had significantly decreased airway resistance and elastance compared to IL-4Rα-/lox littermate controls, as well as reduced airway inflammation, mucus hypersecretion and airway eosinophilia. IL-4 and IL-5 production by CD4+ T cells in the lungs was significantly reduced in both LckcreIL-4Rα-/loxand IL-4Rα-/- mice compared to littermate controls, whereas IL-13 production was decreased only in IL-4Rα-/- mice. Interestingly, CD4+ T cells in LckcreIL-4Rα-/lox mice had significantly increased IL-17 production. Collagen deposition appeared in areas of inflammation around airways and blood vessels and was increased in all OVA-challenged mouse strains compared to the PBS control group.
Conclusions: In summary, our results show that signalling through the IL-4Rα on CD4+ T cells plays an essential role in airway hyperreactivity and allergic airway inflammation.
