Linette Willemsen

Linette is an expert in Mucosal Immunology and uses human in vitro models and murine in vivo models of allergic diseases. Linette did her PhD research in the field of Medicine on the topic of Inflammatory Bowel Disease when she was employed at Numico Research B.V. (now Nutricia Research B.V.) in collaboration with the Department of Gastroenterology and Hepatology at the Academic Medical Centre of the University of Amsterdam (promotor Prof. MD. S. van Deventer). After her PhD she joined the group of Pharmacology as a post doc in 2005 and is assistant professor since 2010. She was co-promotor for 5 PhD students working on the topic of Food Allergy (in vitro and in vivo) or Asthma and is currently guiding 2 PhD students. Linette obtained her BKO in 2009 and SKO research qualification in 2015. Linette is member of the Board of the Scientific Committee of the Figon Dutch Medicine Days since 2015 and was for four years member of the Spring Meeting Committee of the Dutch Pharmacology Society (chair in 2016). She also represents UIPS in the board of the Utrecht Centre for Food Allergy in collaboration with colleagues of TNO-life sciences, the Utrecht Medical Centre Utrecht (UMCU) and the Institute for Risk Assessment (IRAS) of the University of Utrecht (since 2013) and participates in the Future Food consortium and international Cost Action Imparas (allergy risk of novel foods) (both since 2014). Linette Willemsen collaborates with Nutricia Research B.V. within a strategic alliance since 2005.

Research

Linette studies mechanisms underlying prevention and/or treatment of allergy using dietary intervention with non-digestible oligosaccharides (NDO) or n-3 long chain polyunsaturated fatty acids (LCPUFA). For this purpose effects of these bioactive dietary components are studied in human in vitro models and these results are translated to murine models for Food Allergy and Asthma. A monolayer of intestinal epithelial cells forms the interface between the intestinal content and the underlying mucosal immune system and may play a pivotal role in mucosal immune modulation via dietary components. Therefore a transwell co-culture model of human intestinal epithelial cells (IEC) and mixed lymphocytes was developed to study the cross-talk between these cells (see http://www.uu.nl/organisatie/3rs-centre-uls/3vs/3v-interviews). Using this co-culture model, bacterial CpG DNA (a Toll like receptor 9 ligand) combined with NDO was found to effectively drive away from the allergic phenotype of the underlying immune cells by increasing epithelial release of galectin-9, a soluble type lectin known to neutralize IgE and instruct regulatory T-cells. Similarly, in cow’s milk allergic mice fed a diet containing NDO and a beneficial bacterial strain, it was observed that intestinal and serum galectin-9 levels were increased in correlation with the suppressed allergic symptoms. These findings showed the translational value of the co-culture model. The co-culture model is now further extended using immune cells of peanut or cow’s milk allergic donors and NDO are now used as adjunct therapy in allergen specific oral or subcutaneous immunotherapy in food allergic mice (STW NUTRALL). The epithelial lining, both in the intestine and the lung, can provide signals that trigger allergic sensitization (e.g. the release of IL-33). Interestingly specific NDO suppress the pulmonary inflammatory response in mice affected with house dust mite asthma and reduce tissue IL-33 levels via mechanisms involving regulatory T-cells. Beyond NDO also n-3 LCPUFA, such as present in fish oil, effectively suppress food allergy in mice via induction of regulatory T-cells which was confirmed in an adaptive transfer study. In in vitro studies we have shown that n-3 LCPUFA also enhance epithelial barrier integrity and suppress the release of inflammatory mediators by mast cells. Linette aims to focus future studies on the quality of fish oil in relation to its efficacy in Food Allergy and/or Asthma and apply the Pharma/ Nutrition approach with n-3 LCPUFA as a dietary adjunct therapy.

Selected publications

  1. van den Elsen LW, van Esch BC, Hofman GA, Kant J, van de Heijning BJ, Garssen J, Willemsen L.E. Dietary long chain n-3 polyunsaturated fatty acids prevent allergic sensitization to cow's milk protein in mice. Clinical and Experimental Allergy. 2013;43(7):798-810.

  2. de Kivit S, Kraneveld AD, Knippels LM, van Kooyk Y, Garssen J, Willemsen LE. Intestinal epithelium-derived galectin-9 is involved in the immunomodulating effects of nondigestible oligosaccharides. Journal of Innate Immunity. 2013;5(6):625-38.

  3. de Kivit S, Saeland E, Kraneveld AD, van de Kant HJ, Schouten B, van Esch BC, Knol, J., Sprikkelman, A. B. van der Aa LB, Knippels LM, Garssen J, van Kooyk Y, Willemsen LE.  Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans. Allergy. 2012;67(3):343-52.

    More information can be found on her staff page