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Eosinophilic and neutrophilic inflammation in different asthma phenotypes, with special focus on T lymphocytes

Apostolos Bossios, Margareta Sjöstrand, Carina Malmhäll, You Lu
Krefting Research Centre, Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden

Background

Asthma is a chronic lung disease that leads to significant morbidity and mortality characterized of airway inflammation, intermittent airway obstruction, bronchial hyperresponsiveness, mucus hypersecretion and smooth muscle hypertrophy. The disease is heterogeneous in terms of pathophysiology and phenotypes contributing to the difficulty in both studying and treating asthma. Characterization of asthma phenotypes has become an important scientific task that has to be approached by both clinical and research sight. Airway inflammation is a hallmark of asthma and different cellular inflammation is a key feature for categorization of different asthma phenotypes affecting both residual cells but most strikingly an increased number of effector cells, mainly eosinophils but also neutrophils. T-lymphocytes of different subsets as Th1, Th2, Th17 and T regulatory cells are probably the most important cells orchestrating both the initiation as well as the down-regulation of inflammation by secretion of different cytokines, showing plasticity by affecting each other’s differentiation and function.

Aim

The key focus of this project is to evaluate the relationship between different T helper cell, inflammation and circulating eosinophils and/or neutrophils in different asthma phenotypes. A second aim is to relate these findings with clinical characteristics of the already establish asthma phenotypes

Method

Asthmatic patients will be characterized by low or high blood eosinophilia and the presence of high/low neutrophilia. In a parallel study smoking status will be considered. Groups will be characterized based on their status during screening in an ongoing cohort study of Västra Götaland. A futher characterization of circulating Th cells and eosinophils/neutrophils will be done by advanced flow cytometric analysis and RT-PCR. The inflammatory milieu will be characterized by evaluation of the circulating cytokines and chemokines. Above results will be correlated to the asthma phenotypes.

Importance

Understanding of the underlying mechanisms of inflammation in phenotypes of asthma may lead to improved treatments and putatively future cures.

T regulatory cells, that express transcription factor FOXP3

T regulatory cells, that express transcription factor FOXP3

Stimulated T-helper cells, type 2, that express transcription factor GATA 3

Stimulated T-helper cells, type 2, that express transcription factor GATA 3

Page Manager: Madeleine Ahrnens|Last update: 11/17/2009
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