Akdis
Fakultäten » Medizinische Fakultät » SIAF - Schweizerisches Institut für Allergie- und Asthmaforschung » Prof. Dr. Cezmi A. Akdis » Akdis
Current research project
| Title / Titel | T cell interaction with tissue cells in allergic inflammation | ||
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| Abstract (PDF, 14 KB) | |||
| Summary / Zusammenfassung | It has been estimated that 300 million people suffer from asthma and more than 250,000 people die every year in the world. Asthma is characterized by airway inflammation, airway hyperresponsiveness and airway obstruction. Airway obstruction is usually reversible in mild and acute asthma. When airway inflammation is not adequately treated, it results in permanent irreversible structural changes in the airways, so called airway remodeling. Airway remodeling can be defined as an excessive repair processes following repeated airway injury, whose features are increased airway smooth muscle (ASM) mass, inflammatory cell infiltration, subepithelial fibrosis, mucus metaplasia and bronchial angiogenesis. Increased ASM mass, which consists of hyperplasia, hypertrophy and migration of ASM cells is the most important component of airway remodeling process in asthma. Strategies for the treatment are being developed, which are focused on three mechanisms including decreased ASM cell proliferation, augmented ASM cell apoptosis, and reduced ASM cell migration into the smooth muscle layer. It is difficult to treat increased ASM cell mass because no medication sufficiently works in clinical use so far. Activated T cells and effector functions in the allergic inflammatory organs represent essential immunological events in the pathogenesis of asthma and atopic dermatitis (AD). Tight junctions (TJs) are the most apical component of plasma membrane of polarized epithelial and endothelial cells and serve as regulators of permeability and integrity of the epithelium. There is clear evidence that epithelial TJs and ASM cells and fibrocytes are regulated by T cells. This project is aiming to develop new pathophysiological insights into interaction of the immune system cells, particularly recently identified effector T cell subsets, such as Th9, Th17, Th22 as well as T regulatory cells and their cytokines with resident tissue cells in allergic diseases. The following investigations will be focused and their in vivo relevance in humans will be analysed. 1)Tight junctions and leaky epithelium contributes to disease severity and is regulated by T cell subsets. 2)Treg cells may open tight junctions and lead to drainage of the inflammatory cells towards lumen from bronchial parenchyma. 3)Regulation of skin keratinocyte tight junctions plays a role in eczema formation in AD. 4)The increase in ASM content can explain the mechanical consequences of airway remodeling, such as airway luminal narrowing and the permanent reduction of the airway caliber and is regulated by T cell subsets. 5)Skin and lung fibroblast interaction with T cell subsets plays a role in AD and asthma pathogenesis. | ||
| Keywords / Suchbegriffe | T regultory cells, Tight junctions, Asthma, Bronchial epithelial cells, Keratinocytes, Smooth Muscle, Cytokines, Atopic dermatitis, T cells | ||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung) |
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| Duration of Project / Projektdauer | Oct 2010 to Sep 2013 |