Project

Protein crystals in asthma : markers or makers of eosinophilic inflammation

Duration
01 January 2017 → 31 December 2020
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Natural sciences
    • Other biological sciences
    • Other natural sciences
Keywords
crystals asthma
 
Project description

Asthma is a chronic inflammatory disease that affects up to 300 million people. Allergic asthma is controlled by a type 2 immune response rich in Th2 cells, innate lymphocytes type 2, basophils, alternatively activated macrophages and mostly eosinophils. Since 1850 it is known that the airways of asthmatics contain Charcot-Leyden crystals. Charcot-Leyden crystals are unconventional crystals as they are made up of the eosinophil-derived protein galectin-10, that has a very high propensity to spontaneously crystalize in th extracellular space. Mice do not express the galectin-10 protein. However, in mice, sites of eosinophilic airway inflammation are also rich in crystals, but these are made up of the chitinase like protein Ym1 made by macrophages. Traditionally, the presence of these crystals is merely seen as a marker of severe eosinophilic airway inflammation. Here we propose the original hypothesis that these crystals do have a function and promote and maintain the disease. We will investigate the function of these crystals in highly advanced and translational models of allergy to the relevant allergen house dust mite, and we will investigate what might be the evolutionary driving pressure for forming protein crystals at sites of eosinophilic airway inflammation. Through novel tool creation and multidisciplinary research, we envisage the unmasking of a novel drugable pathway in asthma and unraveling of a new pathway underlying development of type 2 inflammation.