Asthma is a heterogeneous chronic inflammatory lung disease that remains a major cause of human morbidity. While treatment with corticosteroids helps many asthma patients to sufficiently suppress symptoms, a substantial group presents as therapy-resistant and suffers from uncontrolled asthma and frequent exacerbations triggered by respiratory infections. This project employs a combination of flowcytometry, cell culture, epigenomics technology and single cell transcriptomics applied to severe therapy-resistant asthma patient samples and an experimental animal model of virus-induced asthma exacerbation. Special emphasis will be placed on CD8+ T cells, a type of immune cell that we hypothesize is implicated in steroid-resistant severe asthma. This approach will provide novel insights into the mechanisms underlying uncontrolled asthma and exacerbations, aiming to pinpoint novel therapeutic approaches for ameliorating disease burden in therapy-resistant asthma patients.
This project aims to provide new knowledge on the role of CD8+ T cells in severe asthma and uncover molecular features specific to patients with therapy-resistant disease.