Project: Understanding Heterogeneity of Eosinophils in Airway Disease

2018-01-01 – 2021-12-31

Abstract

Asthma, Chronic Obstructive Pulmonary Disease, and Chronic Rhinosinusitis are highly
prevalent and heterogeneous airway diseases that cause high morbidity and substantial socioeconomic
burden worldwide, and for which there is no definitive cure. Eosinophils (Eos)
accumulate in these diseases, and are thought to cause harm, which has lead to development
of drugs targeting Eos. However, our consortium recently discovered that there are different
subsets of Eos, some of which have immunoregulatory beneficial roles. The interdisciplinary
U-HEAD network of excellence consists of internationally established basic and clinical
translational scientists in this field. We hypothesize that functions previously attributed to Eos
like toxic granule release, antiviral effects, antigen presentation and immunoregulation are
performed by distinct Eo subsets. U-HEAD will study the function of Eo subsets in tissue
homeostasis, antigen presentation, immune regulation and diseases of the lung and nose.
Eosinophil heterogeneity will be revealed in mice and humans using unbiased single cell
analysis and bioinformatics, to find better (bio)markers of subsets. Cutting edge technologies
applied to relevant disease models in transgenic and cell-specific knockout mice, ex vivo cell
culture models and freshly isolated and biobanked human samples, will deliver definitive and
clinically relevant answers to how subsets of Eos contribute to airway disease and who
benefits best from Eo targeted therapies