Our research team focuses on interactions between specifically manufactured biomedical nanoparticles and antigen presenting cells of the respiratory tract. While we are routinely using flow cytometry as an ideal approach to quantify particle-cell interactions as well as phenotypic and functional changes in immune cells upon particle exposure, there is a constant and growing need for novel approaches to detect and track nanoparticles in situ inside the tissue or even inside single cells in order to determine the fate of promising nanocarriers or to clarify possible pathways of immunomodulation.
Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an increasing prevalence, an unknown aetiology and a current lack of treatment options. The median survival of this disease is three to five years after diagnosis.
For some decades already, animal models in the context of IPF are well described. The most common is the bleomycin induced lung injury mouse model (BLM), which is employed in our current project.
Many different subsets of immune cells were shown to be affected in the course of IPF and/or the BLM model. Pulmonary T cells with regulatory T cells (Tregs) in particular, are currently amongst the most frequently discussed immune cell subsets with a potential to considerably affect the course of IPF. Tregs are known to be involved generally in the immune tolerance by dampening immune responses of the adaptive immune system. However, in context of IPF, recent findings regarding involvement of Tregs were controversial in human IPF and BLM animal models alike.
In the current project, we aim to investigate T cell subsets within different organs and compartments in the BLM mouse model in concomitance with other immune cells in order to draw a clear map of changing patterns (I.e. activation and function) at different time points after bleomycin challenge. Thus, analysis with flow cytometry, an extensive RNA profiling and a monitoring with laser scanning microscopy in pulmonary CD3+ T cells is done. Findings obtained are analysed in order to develop a novel treatment strategy based on nano carriers (e.g. liposomes) or transfected immune cells. Nanocarriers or cells will carry hepatocyte growth factor (HGF) since anti-fibrotic and immunomodulatory effect of HGF has previously been shown by Gazdhar and co-workers.