IgE-independent Stimulation of Mast Cells in Cholinergic Urticaria

• Applicant: Professor Dr. Martin Metz, since 11/2024
• Subject Area: Clinical Immunology and Allergology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 540910088

This project will be conducted by two partners. Partner 1 will be from Türkiye, Koç University, leaded by Prof. Dr. Cansın Saçkesen and Partner 2 will be from Germany, Charité-Universitätsmedizin Berlin, Institute of Allergology IFA, leaded by Prof. Dr. Marcus Maurer and coordinated by both Prof. Dr. Emek Kocatürk and Dr. Jörg Scheffel. Previous findings provide us a glimpse into the pathomechanism of Cholinergic Urticaria (CholU). Yet a detailed and complete mechanistic explanation is missing. In this project, our main question is: ?How acetylcholine stimulates mast cells to cause degranulation?? We will try to investigate this phenomenon at expression (RNA), protein, and genomic levels. Our model would be acetylcholine stimulation of reported human mast cell lines. Our aim would be to mimic the CholU and reveal the whole and detailed molecular and genetic mechanism of acetylcholine stimulation on mast cells that results in degranulation and histamine release eventually causing hives in cholinergic urticaria patients. Our methodology will include following techniques: quantitative real time polymerase chain reaction (qPCR), immunoblotting, flow cytometry, ELISA, and RNA sequencing. At first, we would like to reveal the changes that happen in the mast cells in CholU setup at the expression level. To this end, investigating the expression level changes of certain genes via qPCR experiments and more importantly, the expression levels of whole genome upon acetylcholine stimulation of mast cells with RNA sequencing will be completed. After this second round of this project starts which is revealing the changes at protein level. This will be completed with immunoblotting technique (i.e., Western Blot). The expectation is to observe the similar patterns that was observed at mRNA level. Third round of this project focuses on the receptor levels on mast cells. Flow Cytometry technique will be utilized for this end. The expectation would be to observe the changes happening upon mast cell stimulation in CholU setup. The last round of this project would be analyzing the released mediators from mast cells upon activation. The expectation is to detect proinflammatory cytokine release upon activation. The project planning enables a complementary work package organization, enabling maximal output from this collaboration. The exchange of knowledge and experience between scientists in two centers in Türkiye and Germany will result in high level of output and synergy in the field of Cholinergic Urticaria.

• DFG Programme: Research Grants
• International Connection: Turkey
• Partner Organisation: TÜBITAK The Scientific and Technology Research Council of Turkey
• Cooperation Partner: Professorin Cansin Sackesen, Ph.D.
• Ehemaliger Antragsteller: Professor Dr. Marcus Maurer, until 10/2024 (†)