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Study neutrophil function during RSV-bronchiolitis

Tuesday 30 May 2017

Study neutrophil function during RSV-bronchiolitis
Prof.dr Louis Bont

Project
This study aims to provide proof of principle that the LAIR-1 inhibitory receptor is a therapeutic target for the treatment of RSV bronchiolitis. With an estimated 64 million cases annually (World Health Organization), RSV bronchiolitis is responsible for significant infant morbidity. There is desperate need for an effective treatment for severe cases of RSV bronchiolitis. Neutrophilic granulocytes dominate the local immune response during RSV bronchiolitis. These neutrophils are required for disease resolution, but they also cause extensive tissue damage, in fact causing many of the symptoms of severe disease. Neutrophils are regulated by various inhibitory receptors, which could, therefore, serve as target for intervention.
First, our group found a relationship between single nucleotide polymorphisms (SNP) of the leukocyte-associated Ig-like receptor (LAIR)-1, of which the natural ligand, collagen, is abundantly available in the lungs. Second, pilot experiments have shown that LAIR-1 is expressed on neutrophils in the lungs and that this expression is upregulated during severe RSV bronchiolitis. Third, we have shown that blocking LAIR-1 in a mouse model leads to greater neutrophil influx into the lungs. Using a cross-sectional study we will compare LAIR-1 expression in blood and BAL of neonates without RSV compared to RSV bronchiolitis patients. If we can confirm the importance of LAIR-1 in controlling neutrophil pathology during RSV bronchiolitis, LAIR-1 may provide an attractive therapeutic target for severe RSV bronchiolitis.

Techniques
isolation of neutrophils from peripheral blood and sputum, NETosis assays, oxidative burst assays, FACS, cellsorting , RNA isolation.

Duration
6 or 9 months starting somewhere between September and November (the RSV season starts in December).

Contact
S.B.Besteman, s.b.besteman @umcutrecht.nl 088 7775 457
Prof L.J. Bont, l.bont@umcutrecht.nl

References
Geerdink, R. J., Pillay, J., Meyaard, L., & Bont, L. (2015). Neutrophils in respiratory syncytial virus infection: A target for asthma prevention. Journal of Allergy and Clinical Immunology, 136(4), 838847. doi:10.1016/j.jaci.2015.06.034