Institute for Stroke and Dementia Research

Project description

1. Function of MIF proteins in chronic versus acute inflammation: focus on T cells

MIF proteins are inflammatory cytokines with chemokine-like activities that play a well-described pivotal role in the pathogenesis of atherosclerosis, other cardiovascular conditions, and various acute and chronic inflammatory diseases. Overall, MIF is considered to be an innate cytokine/chemokine which exerts most of its roles by controlling cells of the innate arm of the immune system. However, recent evidence also suggests a critical role for MIF and its homolog MIF-2 in the control of T-cell activity. In the project, these novel unexpected effects will be studied and in both chronic (atherosclerosis) and acute (stroke and acute respiratory distress syndrome, ARDS) experimental disease models. Systematic comparison of MIF, MIF-2, and their receptors in these models will lead to an in-depth mechanistic exploration of the MIF/T-cell axis and offer leads to new therapeutic approaches. The thesis will be embedded into this task and cover a substantial part of these project aims.

2. MIF-family proteins in ischemic stroke

MIF proteins are inflammatory cytokines with chemokine-like activities that play a well-described pivotal role in the pathogenesis of atherosclerosis, other cardiovascular conditions, and various inflammatory diseases. Initial reports have suggested that MIF (MIF-1) plays a causal role in ischemic stroke, but the underlying mechanism and the role of novel MIF family members and the interplay with the MIF receptors in unclear. Interestingly, intracellular activities of MIF have recently been implied and sex-specific effects have been observed. We will unravel the mechanism behind these observations and characterize the role of MIF proteins and their receptors in their entirety in ischemic stroke. The thesis will be inherently embedded into this task and cover a substantial part of these project aims.