The German Society for Allergology and Clinical Immunology (DGAKI) awards the "Förderpreis für Allergen Immuntherapie" every year, donated by Allergopharma GmbH & Co. KG. This time, the DZL-PI prize of 5,000 euros is awarded to Dr. Ulrich Zißler from the Center for Allergy & Environment (ZAUM) of the Technical University of Munich (TUM) and Helmholtz Zentrum München (HMGU). The award ceremony took place during the German Allergy Congress in Dresden.
The DGAKI Award is given for outstanding scientific work in the field of allergology and clinical immunology and serves to promote young, up-and-coming scientists. Papers dealing with diagnostic and therapeutic issues in the field of specific immunotherapy are eligible for an award. Together with his team at the Center for Allergy and Environment (ZAUM, headed by Prof. Dr. Carsten Schmidt-Weber) and the German Center for Lung Research (DZL), Dr. Zißler published a study in the journal "Allergy" about how allergen-specific immunotherapy induces the anti-inflammatory mediator secretoglobin 1A1 in the lower airways and counteracts allergy-associated mediators.
In a clinical study cohort, secreted proteins were shown to be directly regulated by allergen-specific immunotherapy in the lung. The anti-inflammatory process thus initiated directly affects the lung epithelium and influences the release of the inflammatory mediators interleukin-4 and IFN-gamma on the epithelial cells. These secrete proteins in response to these stimuli - key mediators in allergic or viral reactions. "We were able to show both in vivo in induced sputum and in vitro in cell culture that antagonistic regulation takes place by secretoglobin and interleukin-24," summarizes Dr. Ulrich Zißler, lead author of the study along with Prof. Carsten Schmidt-Weber and PD Dr. Adam Chaker. "Interestingly, we were able to see this regulation not only in asthma patients, but also in hay fever patients, who usually have a symptom burden in the upper airways. In doing so, we observed that interleukin-24 was downregulated by secretoglobin, making it a potential biomarker of anti-allergic inflammation and a polarized epithelial response to Th2 stimulation," Zißler added. "We were also able to demonstrate these results in an independent immunotherapy cohort of 57 patients" says PD Dr. Chaker, an otolaryngologist at Klinikum Rechts der Isar, who conducted the recruitment of the cohorts. Ulrich Zißler further explains, "Immunotherapy restored the severely reduced levels of anti-inflammatory secretoglobin in asthmatics and rhinitis patients to the level of healthy control subjects in lung supernatants as well as in nasal secretions and serum samples."
The scientists then tested in cell culture how secretoglobin acts on epithelial cells alone or in combination with an allergic stimulus. To do so, they exposed epithelial cells to the cytokine individually as well as together with house dust mite extract. "Interestingly, a pattern of regulation emerged that we have known from T-cell immunology for many decades," Dr. Zißler states. The authors therefore conclude that the regulation of epithelial cells in allergen-specific immunotherapy is controlled by anti-inflammatory mediators.
"Until now, the role of anti-inflammatory mediators in immunotherapy has only been attributed to cells of the immune system. In our study, we were able to show that the lung epithelium itself plays an active role in the regulation of allergic inflammation. The described mechanism of the epithelial cells shows that one could influence inflammatory processes in the airways even without the immune system, e.g. by inhalative disease," said Zißler.
Origial publication: Allergen-specific immunotherapy induces the suppressive secretoglobin 1A1 in cells of the lower airways