IL-33 and the pathogenesis of airway remodelling in bronchialasthma with focus on severe paediatric asthma

• Applicant: Dr. Ruth Magarethe Grychtol
• Subject Area: Pneumology, Thoracic Surgery ; Immunology ; Pediatric and Adolescent Medicine
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 241276753

Allergic bronchial asthma is one the most common chronic diseases in children. Especially the pathogenesis of severe therapy-resistant asthma of children is not completely understood and therapies are lacking. Research in bronchial asthma in the last years focuses increasingly on the airway epithelium and epithelium derived cytokines in orchestrating allergic airway inflammation and airway remodelling, an important feature of severe asthma. Interleukin-33 is an epithelial cytokine which is an important initiator of acute allergic airway inflammation; however its role in airway remodelling and in paediatric asthma is still unknown. The aim of this project is to explore the role of airway epithelium derived IL-33 in airway remodelling with the help of mouse models of asthma. Airway remodelling will be studied in vivo using mice sensitized with house dust mite extract over several weeks and in vitro using cell cultures. The role of epithelium derived IL-33 in contrast to leukocyte derived IL-33 will be studied in mice with differed expression profiles of IL-33 (expression solely in the airway epithelium and solely in bone marrow derived cells). The role of IL-33 in paediatric asthma in comparison to adults will be studied in a neonatal mouse model of asthma which has already been shown to be suitable as a model for paediatric asthma. Understanding IL-33 and its contribution to airway remodelling and to paediatric asthma might help to develop therapeutic means and preventive strategies, which is especially important for childhood asthma.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Professorin Dr. Clare Lloyd