Schaub Lab

This project aims to disentangle the role of inflammatory regulation (NF-κB and MAPK signalling) during immune maturation in childhood asthma development and its protection via environmental stimulation. Having blood samples from several time points of two birth cohorts and one cross-sectional cohort of children, which are at risk for asthma or protected from asthma offers a unique opportunity to examine immune mechanisms of asthma development. Two central mechanisms of interest are pro- and anti-inflammatory pathways during immune maturation and how these can be modulated in order to prevent the development of childhood asthma.

Multinational study on rural environmental protection for childhood asthma – a central role for dendritic and regulatory B-cells during immune maturation

This multinational study aims to identify central mechanisms of environmental protection for childhood asthma in both Europe and China. By assessing dendritic cells (DC) and regulatory B-cells (Breg) during immune maturation, this project aims to disentangle novel central regulatory hubs which contribute to asthma protection via two strong asthma-protective environments.

The unique chance of having consecutive blood samples of children at several ages of an European birth cohort from the strongest asthma-protective environment, namely farming, available and in parallel recruiting Chinese children from urban HongKong (and Guangzhou) with high asthma prevalence and rural Conghua with low prevalence at age 6 years allows the comparison of asthma-protective mechanisms across Europe and China.

This project aims to disentangle distinct protective immune regulatory mechanisms of A20-mediated effects of dendritic (DC) and regulatory T cells (Tregs) for childhood asthma by stimulation of blood cells with compounds of environmentally distinct areas. The unique natural exposure to two environments strongly protecting from childhood asthma, i.e. farms in Europe and rural areas in China offers the great opportunity to assess underlying immune mechanisms which are distinct from each other.

As A20 (anti-inflammatory) and inflammasome regulation have been shown differentially expressed following different dust stimulation, we will identify the specific role of A20 and inflammasome regulation following environmental exposure with different dusts in cell lines, and isolated cells. We will disentangle specific asthma-protective immune mechanisms via A20-mediated effects of DCs on Tregs through exposure to distinct rural environmental dust in healthy and asthmatic children. We will unravel the effect of environmental dust extracts from different environmental areas (Germany, Finland, China) on T reg-function, methylation, acetylation (FOXP3 promoter), and mTOR signalling. We aim to identify signalling of A20 regulation in DCs and inflammasome activation. We aim to investigate the effect of A20-regulation in DCs and inflammasome activation on Treg-mediated suppression. Finally, in a proof-of-principle experiment, we will assess the effects of dust stimulation on A20-regulation in DCs, inflammasome and Treg regulation in children protected from asthma in comparison to asthmatic children. 

The EFRAIM project prospectively investigated protective factors in early life influencing the development of allergies in birth cohorts conducted in rural areas in five European countries. Detailed information on a great variety of environmental exposures was collected and large biobanks have been established. The mechanisms mediating these protective exposures such as the maturation of immune responses, gut colonisation, the mucosal barrier function and the genetic and epigenetic factors interacting with the environmental exposures were investigated.

Currently, allergic diseases can be managed effectively but not cured. The knowledge about protective exposures early in life can, however, be turned into the development of preventive strategies. The EFRAIM project was expected to produce ground-breaking new insights on protective agents and their mechanisms that can be used to prevent the further development of allergies.

In 2019, the 16 year follow-up of the cohort is starting. 

In terms of disease incidence and mortality, lung diseases are ranked second in the world and are directly or indirectly responsible for every fifth death. The annual cost of lung diseases amounts to 102 billion euros alone for Western Europe. It is expected that the number of aptients and thus also the costs will continue to rise in the coming years. To date, there are no cures for most respiratory dieases- just symptomatic treatments.

Asthma is the most prevalent chronic respiratory disease in childhood and is also very common in adults. Although the clinical manifestations of asthma in children and adults are rather uniform with wheezing, shortness of breath and cough, population-based clinical and genetic studies suggest that asthma is not one disease, but many. Thus, a single “one-size-fits-all” treatment approach is unlikely to work to tackle this important health problem. In order to design personalized treatment approaches for asthma patients, there is urgent need to elucidate the mechanisms underlying the various types of asthma. The decoding of such mechanisms and their translation to the individual patient is the aim of the Disease Area Asthma and Allergy of the DZL.

New Publication by Johanna Krusche, MonikaTwardziok, Katharin Rehbach...Bianca Schaub in Journal of Allergy and Clinical Immunology about TNF-α–induced protein (link).

Kristina Laubhahn (Phd Student at the group of Prof. Dr. med. Bianca Schaub) has been awarded an oral abstract prize for an outstanding oral abstract presentation at the EAACI 2019 conference.
The title was: Pathway analysis - genetic and immunological influences of gene polymorphisms in 17q21 locus on childhood wheeze.

Prof. Dr. med. Bianca Schaub was awarded a professorship of LMU Munich (Heisenberg Professorship of DFG, german research foundation) with the title “Environment and development of immunological tolerance” („Umwelt und immunologische Toleranzentwicklung“) with the focus on the development of allergic diseases. The Heisenberg Professorship, named after the physicist, promotes excellent scientists following criteria of scientific excellence.

Prof. Schaub, Consultant and Deputy Head of the Department of Allergology in the University Children´s Hospital of Munich, Dr. von Hauner Children's Hospital, examines the role of early life immune maturation for the development of allergic disease since numerous years.

The focus of this Heisenberg Professorship comprises the assessment of the environment and the development of immunological tolerance from birth until allergy development in childhood. This will be investigated in several birth and cross-sectional cohorts of children with risk or protection from allergies. To characterize molecular mechanisms of the different phenotypes, a number of methods of „computational medicine“ will be used. The identification of biomarkers for specific therapy strategies for childhood allergic diseases will contribute to develop future prevention studies and clinicial studies with novel biologicals.