Impact of metabolic deviations on immune responses

• Applicant: Yuliya Skabytska, Ph.D.
• Subject Area: Dermatology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421390892

The prevalence of obesity has increased over the past years and epidemiological studies show an association between obesity and various disorders including psoriasis and cancer. Although clinical observations for obesity as a risk for these disorders are clear, the mechanisms by which obesity increases their prevalence remain to be fully elucidated. Beside increased systemic pro-inflammatory mediators, obesity is associated with alterations of immune cell numbers and their functions. Our preliminary results show an increased chronification phase of skin inflammation with polarization towards Th1/Th17 immune response due to obesity. The dysregulation of the immune response was also characterized by quantitative and qualitative changes in different cell populations, including macrophages, CD8+ T cells, γδ T cells, NK cells. It is now known that immune cell phenotype/activation is coupled to profound changes in cellular metabolism and that cellular fate and function are metabolically regulated. The goal of the project is to apply new methods and techniques in order to investigate how systemic metabolic changes influence intrinsic cell metabolism and what are their consequences for immune responses. To this end experiments that will provide a detailed insight into the metabolic programs and immune cell functions will be conducted. In particular, we will investigate, how high cholesterol diet influences NK cell and CD8+ T cell metabolism and functions. The role of Sterol regulatory element-binding protein (Srebp) signaling in NK and CD8+ T cells of high cholesterol diet fed mice will be characterized. Finally, the impact of high cholesterol diet on tumor growth and NK cell and CD8+ anti-tumor responses will be investigated. Thus, this fellowship will provide me with the required skills in metabolic analyses to dissect the role of different metabolic pathways in immune responses and skin inflammation.

• DFG Programme: Research Fellowships
• International Connection: Ireland
• Host: Professor Dr. David K. Finlay