CfA seminar "Migration and Urbanisation: Dissection of allergic reactions in an allergen-saturated environment"
Speaker: Prof. Olaf Rötzschke, Singapore Immunology Network (SIgN), Singapore. Coffee and tea will be served after the seminar.
About the topic
In regions with moderate climate the systematic analysis of allergic reactions is complicated with a broad range of different allergens and the strong seasonal variations influencing the exposure. The tropical-urban environment in turn provides a simplified and yet persistent allergen environment. In a recent study, we could establish that in Singapore almost 80% (!) of the local population had been sensitized by a single allergen, house dust mites (HDM). The environmental penetrance by this allergen is so strong that ‘atopy’ is indicated here in 98% of the cases simply by the response against HDM. Total IgE levels in the plasma correlate directly with the HDM-specific IgE titers, which translates into an incidence of airway allergies ranking among the highest worldwide (asthma: ~15%, allergic rhinitis: ~40%). Notably, migrants coming from mainland China to Singapore develop similar high HDM-specific IgE titers. The induction however requires a period of about 8 years and is accompanied by the manifestation of airway allergies, especially rhinitis. While the overwhelming response to house dust mites represents a serious public health problem, it also provides the perfect research environment for cohort-based studies on the mechanisms and causes underlying allergies.
From the blood samples of more than 600 individuals we established a comprehensive database comprising genetic, epigenetic, transcriptional, functional and phenotypic parameters. A systems biology analysis of these data revealed a number of known and novel targets and identified basophils as a key population in the control of disease manifestation: genetic polymorphisms and phenotypic variations affecting the function and migration of basophils were found to be directly linked to the induction of atopy and/or airway allergies. This includes CD203c, a gene strongly upregulated degranulation, as well as enzymes involved in the synthesis sialyl LewisX, a carbohydrate moiety required for leukocyte extravasion. The crucial role of basophisl was particularly evident in the fact that a functional inactivation of basophils, observed in 10% of the cohort, was associated with a reduced incidence of rhinitis. ‘Basophil anergy’ is caused by a down-regulation of SYK, presumably as result of a subthreshold stimulation by allergen/IgE. It was identified as a mandatory transitional state but can apparently persist for extended periods of time (> 2 years).
About the speaker
Olaf Rötzschke is an expert in cellular immunology, immune regulation and immune genetics. During the past 25 years he published over 100 scientific studies cited in more than 11,000 articles. He studied biochemistry at the universities of Hannover and Tübingen, where he received his PhD in 1993. He started his scientific carrier at the ‘Max-Planck Institute of Biology' in the group of Hans-Georg Rammensee, where he isolated here the first natural T cell antigens and resolved their primary structure. In 1993, he joined the group of Jack Strominger at the ‘Harvard University' to carry out studies on the immune-modulation by CD4+ T cells. In 2000, he moved to the ‘Max-Delbrück-Center' in Berlin, where he focused on antigen-presentation, MHC ligand-exchange and the characterization of regulatory T cells (Treg). He joined the ‘Singapore Immunology Network’ (SIgN) in July 2008. While he continued the work on Treg cells and immune regulation, the focus shifted from ‘pure’ cellular and molecular immunology to more complex cohort-based analysis of immune-regulatory pathways. Besides phenotypic and functional characterization the analysis includes also genome- and transcriptome-analysis. The main research activities are now centered on the characterization of pathways related to allergic reactions. In parallel to systems biology, also a translational project has been launched that assess the potential of adoptive transfer of regulatory T cells in a clinical phase I trial.