Cellular Inflammation and Immune Remodeling in Inflammatory Airway Diseases
Principal investigator; Erjefält, Jonas, Associate Professor,
The present project explores immunological processes causing tissue disturbances and dysfunctions in inflammatory diseases such as asthma, allergic rhinitis and COPD. During these conditions high numbers of granulocytes are recruited into the airways. Release of cytotoxic granule proteins from activated granulocytes is thought to induce the typical tissue damages/dysfunctions seen during active disease. Our focus is on cellular mechanisms by which granulocytes cause tissue disturbances. Leukocyte activities are also explored in relation to damage/repair and remodeling processes in the diseased tissue. Another major theme in our research is exploration of processes involved in the natural, or drug-induced, elimination of tissue granulocytes from the site of inflammation.
Through close collaboration between clinical and preclinical researchers the project investigates activation and elimination of airway granulocytes in patients with asthma, allergic rhinitis and COPD. Using detailed histological analysis granulocyte activities (degranulation, apoptosis/secondery necrosis, and cytolysis) are related to relevant parameters of tissue damage and repair. Animal models are used to allow detailed further studies of selected aspects of the airway inflammation. Another part of the project explores mechanisms for clearance of granulocytes during the resolution of an airway inflammation. In this context we have recently discovered that, rather than by apoptosis,a majority of tissue granulocytes in the conducting airways are cleared through a selective migration into the airway lumen. Identification of cell apoptosis/necrosis and processes initiating transepithelial migration of granulocytes and drug effects on these events are also studied.
The project explores central processes leading to tissue damage and symptoms in asthma, rhinitis, and COPD. As such, the project significantly contributes to a critical unravelling of key pathogenic events in our most common airway diseases. The long-term goal of the project is to generate new strategies for therapeutic intervention.
Link to project homepage: http://
5 recent original publications
Erjefält JS, Persson CG
New aspects on degranulation and fates of airway mucosal eosinophils.
Am J. Respir Crit Care. Med. 2000; 161: 2074-2085
Persson CG, Erjefalt JS
Eosinophil lysis and free granules: an in vivo paradigm for cell activation and drug development.
Trends Pharmacol. Sci, TiPS. 1997; 18: 117-123
Rydell-Tormanen K, Uller L, Persson CG, Erjefält JS
Allergen-exposure of mouse airways evokes remodeling of both bronchi and large pulmonary vessels.
Am. J. Respir. Crit. Care Med.. 2005; 171: 19-25
Uller L, Andersson M, Greiff L, Persson CG, Erjefält JS
Occurrence of apoptosis, secondary necrosis, and cytolysis in eosinophilic nasal polyps.
Am J Respir Care Med. 2004; 170: 742-747
Forssell J, Sideras P, Eriksson C, Malm-Erjefalt M, Rydell-Tormanen K, Ericsson PO, and Erjefalt JS.
Interleukin-2-inducible T cell kinase regulates mast cell degranulation and acute allergic responses
Am J Respir Cell Mol Biol. 2005; 32: 511-520
Further publications here (new window)
|Total financing:||3.1 MSEK||Gov grant for clinical research ("ALF"):||MSEK|
|Total external financing:||MSEK||Natl and intl prioritized grants:||MSEK|