Divergent E1 and E2 epithelial differentiation and associated regulatory mechanisms of IL-20 family members

• Applicant: Professor Dr. Carsten B. Schmidt-Weber
• Subject Area: Clinical Immunology and Allergology ; Pneumology, Thoracic Surgery
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398577603

Allergy affects 20% of the population with an increasing trend. The cause and in particular the mechanism of sensitization are yet unknown. Epithelial cells are playing an important role in this process as they are not only forming a barrier, but also contribute to the first context recognition when the antigen is entering the organism. So far, it was not known that epithelial cells undergo a differentiation that polarizes the cells either to a pro-allergic E2-type or an E2 type that is likely to be important for infections. This kind of phenotype imprinting was observed also for T cells or macrophages. Preliminary evidences suggest that this differentiation also modulates epithelial mechanisms of immune regulation, particularly those of the IL-20 family. This group of genes is suspected in anti-inflammatory responses and could be relevant for reconvalescense following airway inflammation. It is therefore a key objective of the research proposal to explore the epithelial differentiation mechanisms and also whether pluripotent epithelial precursor cells are affected, since these are relevant for the regeneration of the epithelial surface. In fact preliminary data suggest that E2 priming occurs on the basal cell level and that E2 priming is dramatically increased in basal cells of trachea of house dust mite sensitized mice. An impact on this level could have a sustained effect for affected patients. In addition the project wants to elucidate whether the distinct epithelial phenotypes give rise to differential responses to bacterial pathogens that are commonly playing a role in exacerbation of airways diseases such as asthma. The regulation of the IL-20 family is a focus of the study readouts as the mediators are thought to mediate epithelial recovery. Since the airway epithelium is well accessible for novel therapeutics, the proposed research can open novel therapeutic option for allergic airway diseases.

• DFG Programme: Research Grants