Crosstalk of circulating EVs and vascular immune cells

Wider research context: Inflammatory diseases are a major cause of morbidity, disability, and mortality and the most significant cause of death worldwide. Ample evidence suggests that chronic low-grade and sterile inflammation are important contributors to aging. In the physiological context, inflammatory processes are required for host defense, clearance of necrotic cells, wound healing, and tissue regeneration. Dysregulated inflammation, however, can cause tissue damage, organ dysfunction, as well as acute and chronic disease. Research questions and objectives: We will study the immunoregulatory roles of extracellular vesicles in inflammation and their impact on different target cells in the vasculature, in particular on monocyte subsets. Approach and methods: The five PhD projects, which are closely integrated, will focus on the capacity of extracellular vesicles from platelets, red blood cells, and mesenchymal stem cells to modulate the distribution of classical, intermediate, and non-classical monocyte subsets. We will further assess the effect of extracellular vesicles carrying oxidation-specific epitopes on monocyte subsets and we will examine whether the binding of natural antibodies influences their cellular uptake and clearance. We will establish optogenetic cell lines with light-sensitive receptors, namely mesenchymal stem cells with light-inducible Toll-like receptors TLRs 2, 3 and 4, to study the involvement of specific TLRs in modulating monocyte subsets. We will further generate monocytes with light-inducible CD36, as well as TLR 2 and 4 to determine the underlying mechanisms of the uptake and clearance of extracellular vesicles carrying oxidation-specific epitopes. Faculty: The faculty consists of six members with complementary scientific background in sepsis, extracellular vesicles, innate sensing of oxidation-specific epitopes, stem-cell induced immune modulation, as well as optogenetics. It is balanced with regard to senior/junior and male/female members and has long-standing experience in supervising PhD students. Its expertise is documented by the leading role of faculty members in national and international joint research programs, including a CD Laboratory, European projects in FP6, FP7, H2020, and Horizon Europe, as well as a Transatlantic Network of Excellence. Doctoral program: “Extracellular Vesicles in Inflammation - Crosstalk of EVs and Immune Cells in the Circulation” is a PhD program of the University for Continuing Education Krems, the IMC University of Applied Sciences Krems, and the Medical University of Vienna. Established jointly by all partners in conformity with standards for innovative structured doctoral training, it provides a multidisciplinary environment, a clear common research theme, as well as integration of basic science and translational aspects. Added value: This is the first PhD program in Austria focusing on the biological importance of EVs and their functional roles in immunomodulation.