Project Details
TRR 22: Pulmonary Allergies
Subject Area
Medicine
Biology
Biology
Term
from 2005 to 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5486276
During the last decades, allergies have emerged as a group of major diseases with bronchial asthma as the most severe manifestation at the respiratory tract. Although allergies have a marked socio-economic impact, the pathophysiology is still purely understood. There is no causal therapy available, prevention and prediction are still insufficient. It is the aim of this Transregional Collaborative Research Centre to tackle these problems and, eventually, to develop new therapeutic and preventive strategies for allergic disease based on the development of a better understanding of the pathophysiology due to the concerted action of this consortium.
During the last years, the regulation of the allergen-specific immune response has been the focus of many research activities. This has led to a better understanding of the contribution of T-cell subsets and the regulation of IgE-production as an important effector mechanism. However, the process from initiation to chronification is still purely understood. Respiratory epithelium has not only a barrier function, but seems to contribute to the pathogenesis via immuno-modulatory effector mechanism. In this context, the epithelium is the first cell-type which primarily interacts with inhaled allergens and microbial components of the environment. Particularly this chronic microbial exposure (e.g. via inhalation) has been claimed to have important priming effects on immune responses against allergens. As an example, lipopolysaccacharides (LPS) have been best examined in this regard. However, endotoxins are only a model antigen in this context which can have such a protective effect. In addition to such environmental components, genetics also plays a very important role in the development of the allergic phenotype. Major research interests include protein-protein, gene-protein and gene-gene interactions.
The partners from Marburg, Borstel and Munich represent leading scientists, covering the areas of clinical and experimental pneumology, clinical and experimental allergology, epidemiology, microbiology and immunology, biochemistry and genetics.
Recent research data indicate a strong association between the microbial environment and allergy development. Based on these results a better understanding of the cellular and molecular mechanism will be developed. In the second and third funding period this should lead to translational and clinical research activities aimed for novel preventive and therapeutic concepts.
During the last years, the regulation of the allergen-specific immune response has been the focus of many research activities. This has led to a better understanding of the contribution of T-cell subsets and the regulation of IgE-production as an important effector mechanism. However, the process from initiation to chronification is still purely understood. Respiratory epithelium has not only a barrier function, but seems to contribute to the pathogenesis via immuno-modulatory effector mechanism. In this context, the epithelium is the first cell-type which primarily interacts with inhaled allergens and microbial components of the environment. Particularly this chronic microbial exposure (e.g. via inhalation) has been claimed to have important priming effects on immune responses against allergens. As an example, lipopolysaccacharides (LPS) have been best examined in this regard. However, endotoxins are only a model antigen in this context which can have such a protective effect. In addition to such environmental components, genetics also plays a very important role in the development of the allergic phenotype. Major research interests include protein-protein, gene-protein and gene-gene interactions.
The partners from Marburg, Borstel and Munich represent leading scientists, covering the areas of clinical and experimental pneumology, clinical and experimental allergology, epidemiology, microbiology and immunology, biochemistry and genetics.
Recent research data indicate a strong association between the microbial environment and allergy development. Based on these results a better understanding of the cellular and molecular mechanism will be developed. In the second and third funding period this should lead to translational and clinical research activities aimed for novel preventive and therapeutic concepts.
DFG Programme
CRC/Transregios
Completed projects
- A01 - Metagenomic Determinants of Asthma Protection in Environmental Dust (Project Heads Ege, Ph.D., Markus ; von Mutius, Erika )
- A02 - Allergy-protection by diversity: synergistic activation of innate immune mechanisms by individual microbial species (Project Heads Heine, Holger ; Holst, Otto )
- A03 - Gräserpollenallergene als Stimulatoren des angeborenen Immunsystems (Project Heads Petersen, Arnd ; Ulmer, Artur Jochen )
- A04 - The role of TLR9 and TIR8 in the development of allergic lung disease (Project Head Bauer, Stefan )
- A05 - Einfluss Toll-like Rezeptor 2 und 4 spezifischer Stimuli auf die allergische Atemwegsentzündung (Project Head Kirschning, Carsten Jürgen )
- A07 - Drosophila as a model in asthma research (Project Head Roeder, Thomas )
- A08 - Modulation of the asthma phenotype by mechanisms of the innate immune system (Project Heads Bals, Robert ; Vogelmeier, Claus )
- A09 - Rolle von Neurotrophinen in der allergischen Immunantwort der Lunge (Project Heads Nockher, Wolfgang Andreas ; Renz, Harald )
- A11 - Neutrophil-mast cell interactions in allergic asthma (Project Head Petersen, Frank )
- A12 - Ein neuartiger Mechanismus der Aktivierung FceRi-positiver Zellen mit Freisetzung von Th2-Zytokinen durch monovalente Immunglobulin-bindende Faktoren (Project Heads Gibbs, Bernhard Frederick ; Haas, Helmut )
- A13 - Entwicklung BAC (Bacterial Artificial Chromosome) transgener Mausmodelle zur Analyse der Rolle von Dendritischen Zellen in der Pathogenese des allergischen Astmas (Project Head Sparwasser, Tim Dominik )
- A14 - The role of CD8+ regulatory T cells and mast cells in the initiation and chronification of allergic asthma (Project Heads Bulfone-Paus, Silvia ; Orinska, Zane )
- A15 - Identifizierung und funktionelle Analyse von Genveränderungen in den immunregulatorischen Faktoren T-bet, Hlx und GATA3: Auswirkungen auf die Entstehung von Asthma (Project Head Kabesch, Michael )
- A16 - Identification of structural modules within IRF4 which control Th subtype diversification in vitro and in vivo during allergic asthma" (Project Head Lohoff, Michael )
- A17 - B cell-crosstalk in the pulmonary allergic inflammation (Project Head Zemlin, Michael )
- A18 - Epigenetic regulation of pre- and neonatal programming of allergic asthma (Project Heads Pfefferle, Petra Ina ; Renz, Harald )
- A19 - Non-Eosinophilic vs. eosinophilic asthma: phenotypical characteristics and gene expression (Project Heads Bals, Robert ; Vogelmeier, Claus )
- A20 - B cellular immune mechanisms of specific immunotherapy in IgE-mediated respiratory allergy (Project Heads Hertl, Michael ; Pfützner, Wolfgang )
- A21 - The role of the anaphylatoxins C3a and C5a in the pathogenesis of experimental allergic asthma (Project Head Köhl, Jörg )
- A22 - Identification of novel biomarkers and underlying immune mechanisms for allergic and non-allergic asthma in childhood: prediction of outcome and translation to clinics (Project Head Schaub, Bianca )
- A23 - Allergy-suppressive properties of helminth antigens and transgenerational effects of helminth infection on allergic airway inflammation (Project Head Prazeres da Costa, Clarissa )
- A25 - Epithelial control of allergic sensibilization by IL-22 (Project Head Schmidt-Weber, Carsten B. )
- A27 - Dissecting the function of TGF-â in allergic asthma (Project Head Buch, Thorsten )
- Z01 - Platform for the isolation of natural aeroallergens as well as cloning and expression of their recombinant equivalents (Project Head Petersen, Arnd )
- Z02 - Animal models for endotypes of allergic airway inflammation (Project Head Garn, Holger )
- Z03 - Service Platform Functional Genomics (Project Heads Buch, Thorsten ; Legatzki, Antje )
- Z04 - Central Tasks (Project Head Renz, Harald )
- Z05 - Imaging methods for functional analysis of cellular dynamics in allergic asthma (Project Head König, Peter )
- Z06 - Mass Spectrometry Platform (Project Head Schwudke, Dominik )
- Ö - Öffentlichkeitsarbeit der DFG-SFB/TR-Aktivitäten auf dem Gebiet der allergologischen Forschung (Project Head Renz, Harald )
Applicant Institution
Philipps-Universität Marburg
Co-Applicant Institution
Ludwig-Maximilians-Universität München; Technische Universität München (TUM); Universität zu Lübeck
Participating Institution
Forschungszentrum Borstel
Leibniz Lungenzentrum
Leibniz Lungenzentrum
Participating University
Christian-Albrechts-Universität zu Kiel
Spokesperson
Professor Dr. Harald Renz