GELLES Katharina

Molecular and Functional Analysis of CD39 Expression in CD4⁺ T-Cells

CD39 is an ectoenzyme expressed on various cells including endothelia, macrophages, B-cells and a subset of regulatory T-cells (Treg). CD39⁺ Treg show an enhanced suppressive potential in comparison to CD39^- Treg. This is due to the fact that adenosine, generated by hydrolysis of adenosine triphosphate (ATP) from CD39 and CD73 on Treg, binds the A_2A-receptor on effector T-cells leading to a suppression of effector-functions. A multitude of studies shows a correlation between CD39-expression on Treg in various diseases. For example, Loza et al. demonstrated that in Lupus erythematosus, CD39 on Treg was almost absent. The authors supposed that this functional defect of Treg could be important for the loss of peripheral tolerance which leads to the development of this autoimmune disease. In contrast, Huang et al. demonstrated that high-levels of CD39⁺ Treg significantly correlated with a poor prognosis in sepsis patients. Schuler et al. showed that CD4⁺CD39⁺ T-cells seem to be accumulated in blood and tumor tissue of cancer patients. Our preliminary data also showed a strongly increased number of CD39 expressing Tregs in tumor tissue compared to healthy tissue in three colon carcinoma patients. We also observed a decreased CD39-expression on regulatory T-cells in blood of patients with Takayasu-arteritis. Taken together, these studies and our preliminary data highlight the importance to understand the regulation mechanism of CD39 for a better comprehension of immunosuppressive mechanisms. This knowledge could lead to improved treatment strategies for various diseases such as autoimmune-diseases, infections and cancer.
The aims of the project are

• Identification of factors which regulate CD39-expression in CD4+ T-cells, especially in regulatory T-cells.
• Analysis of CD39-expression and regulation factors in blood of healthy donors in comparison to various diseases including vasculitis (Takayashu arteritis and giant cell arteritis) and in tissue of colon carcinoma patients.

Methods and Skills:

cell culture; FACS; real time PCR; quantitative PCR; cloning; ELISA

Publications:

Muqaku B, Tahir A, Klepeisz P, Bileck A, Kreutz D, Mayer RL, Meier SM, Gerner M, Schmetterer K, Gerner C. Coffee consumption modulates inflammatory processes in an individual fashion. Mol Nutr Food Res 60: 2529-2541, 2016