Description of Research Activities
Our group conducts research along three intertwined research lines that all relate to advanced histological assessments of inflammatory airway diseases. All research lines take advantage of our unique collection of validated human tissue samples from patients with inflammatory airway disorders (allergic rhinitis, asthma, chronic obstructive pulmonary disease COPD, cystic fibrosis) and state-of-the-art methodology for advanced histological explorations. Our projects are throughout carried out with a translational approach that includes close collaboration with Dept of Respiratory Medicine/Thoracic Surgery, Lund University and leading Pharmaceutical companies.
Our major research lines are summarized as:
- Characterization of Cellular Tissue Inflammation and its Relation to Tissue Damage, Remodeling and Disease Severity
- Phenotyping of Mast cells in Inflammatory Airway Diseases
- Activation and Elimination of Granulocytes in Inflammatory Airway Diseases
Through our validated protocols for identifying all major leukocyte subtypes within individual tissue samples we aim to map distinct patterns of cellular inflammation and study how these relate to local histopathological alterations including airway remodeling (e.g. epithelial damage, hyperproliferation of structural cells, goblet cell hyperplasia, enlarged smooth muscle mass, fibrosis, emphysema etc.). Apart from providing a valuable characterization of the inflammatory picture the goal is to get insight into the pathogenic role of individual leukocytes, or combination of leukocytes (“leukocyte patterns”), for the overall histopathological picture, disease severity and symptoms. Since patterns of cellular inflammation or tissue disturbances readily can be correlated to any pro-inflammatory mediator our approach has turned out to be a powerful tool in target validation. Another important area is to explore the effect of novel and current therapeutic strategies on inflammatory picture in the diseased tissue.
Apart from their reputed role in allergic disorders, mast cells (MC) have remained poorly studied in human lungs. Yet, with their newly ascribed roles in innate immunity, immune regulation and remodeling it can be envisioned that MCs take active part also in non-allergic inflammatory conditions such as COPD, cystic fibrosis and IPF. We recently started to characterize mast cell populations in normal human lungs and found a remarkable heterogeneity that goes far beyond classical divisions into MCT and MCTC populations. Within this project we recently identified novel site-specific MCT and MCTC subtypes with distinct molecular expression in bronchi, bronchioles, pulmonary arteries/veins and the alveolar region. Further characterization of these novel MC “subtypes” in the normal lung and their activation status in COPD, CF, asthma, and IPF is currently in progress.
Granulocytes are important effector cells of the immune system and produce tissue disturbances by several mechanisms. We previously discovered receptor-mediated eosinophil cytolysis (ECL) as a novel pro-inflammatory mechanism that together with piecemeal degranulation account for the release of cytotoxic proteins from eosinophils during allergy. For neutrophils, which are extremely short-lived and readily undergo apoptosis, we recently discovered that, in areas of intense inflammation, abundant apoptotic neutrophils escape phagocytosis and disintegrate in a pro-inflammatory process termed secondary necrosis. The pathogenic consequences and therapeutic potential of inhibiting these processes, while enhancing the silent physiological elimination, now await further exploration.