Dr. Ulrich Zissler and Prof. Dr. Carsten Schmidt-Weber, Source: Helmholtz Zentrum München
The team of Prof. Carsten Schmidt-Weber and Dr. Ulrich Zissler from the Center of Allergy & Environment (ZAUM) at Helmholtz Zentrum München and TU München discovered that the epithelium of the respiratory tract also undergoes a development which so far has only been known to exist in immune cells influenced by allergens. In the scope of a project run by the German Center for Lung Research (DZL) scientists treated epithelial cells of the respiratory tract with the allergy messengers interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) and observed how genetic activity changed.
“Interestingly, a regulation pattern emerged which we have known for many decades to exist in T-cell immunology as the Th1/Th2-paradigm*,” Zissler, first author of the study, comments the results. For—just as it has already been known for cells of the immune system—IL-4 was capable of activating the genes of the so-called Th2-immune response which contributes to the development asthma**. IFN-gamma counteracted this process as it facilitates the transcription of Th1-genes.
The authors exemplarily describe the molecule interleukin-24 (IL-24) which is upregulated by IL-4 and downregulated by IFN-gamma . According to the researchers, IL-24 might someday serve as a biomarker of allergy-induced airway epithelium inflammations.
Mechanism confirmed in hay fever patients
In order to verify the relevance of their results, the researchers also tested the results in rhinitis patients***. It showed that the effect could be observed in the nasal mucosa of the patients as well. The authors concluded that the regulation of epithelium cells in allergic disease ends in some kind of fingerprint of the allergy. Further studies must now reveal whether this imprint impedes immunity to infections or other reactions to the environment and thus might result in additional problems for allergic patients, the researchers infer.
“The Th1/Th2-paradigm has been limited exclusively to T-cells so far. The mechanism including epithelial cells which we now discovered therefore gives us a more profound insight into the complexity of immune response and approaches to develop therapies for allergic diseases,” says ZAUM director Schmidt-Weber.
* The Th1/Th2-paradigm regards IL-4-producing T-helper cells of type 2 (Th2) as antagonists of the Th1-cells, and Th2 cells are accordingly classified as the driving force of allergic reactions.
** Interleukin-4 is an essential messenger associated with allergic inflammations which also leads to allergic asthma and inhibits the tolerance to allergens by way of a Th2-immune response, as the previous studies were able to show.
*** Allergic rhinitis, or pollen-induced hay fever, is an allergy-mediated inflammation of the nasal mucosa. It is often accompanied by other diseases of the respiratory tract, such as sinusitis (inflammation of the maxillary sinuses) and asthma.
Zissler, UM. et al. (2015). Interleukin-4 and IFN-gamma orchestrate an epithelial polarization in the airways. Mucosal Immunology, DOI: 10.1038/mi.2015.110
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.
The Center of Allergy & Environment (ZAUM) in Munich is a joint undertaking by the Helmholtz Zentrum München and the Technical University of Munich (TUM). This cooperation, which is the only one of its kind in the German research landscape, is dedicated to interdisciplinary basic research and forms a link between clinicians at the hospital and clinical research staff at the university. Thanks to this approach, findings about the mechanisms that lie behind allergies are translated into preventive and therapeutic measures. The development of effective, individually tailored treatments enables better care to be provided for allergy-sufferers.
Dr. Ulrich Zissler, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Center of Allergy & Environment, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 4140 3472 – E-mail
Prof. Dr. Carsten Schmidt-Weber, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Center of Allergy & Environment, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 4140 3451 – E-mail