Our mission is to use the heterogeneity of myeloid cells (MCs) as an in vivo sensor to track inflammatory responses and as a target for therapeutic intervention (Figure 1). Recent evidence (including our own) reveals that tissue-associated MCs contain different subpopulations with different ontological origin, including embryonic yolk sac and fetal liver-derived resident macrophages and adult bone marrow-derived recruited MCs (mainly monocytes, monocyte-derived macrophages, neutrophils and dendritic cells). Evidence is mounting that these MC subpopulations perform distinct functions in health and disease. Thus, we focus on studying (epi)genomics, transcriptomics, proteomics, metabolomics and functional heterogeneity of different MC subpopulations present in selected inflamed tissues, in particular in tumors (tumor-associated macrophages, myeloid-derived suppressor cells and dendritic cells), the liver (Kupffer cells), and the brain (microglia and barrier-associated macrophages or BAM).
Based on markers that allow a discrimination between selected MC subpopulations, we fully invest in the development of innovative tools to visualize and modulate the in vivo differentiation, recruitment and function of selected MC subpopulations in inflamed tissues. These include in particular the identification of markers for different tumor-associated macrophage or dendritic cell populations, as well as Kupffer Cell- and microglia/BAM-specific markers, to generate transgenic (knock-in) mice allowing the tracking and ablation of selected MC populations. Such tools will reveal the role of these MCs in homeostasis and in distinct models of tumor growth and liver or brain injury. We also aim to develop original strategies to overcome inflammation-associated immunopathology of infectious and non-infectious diseases. In this regard, we fully exploit the strategic advantage of nanobodies, i.e. camelid-derived single-domain antibody fragments, and their engineering platform as tools for in vivo MC-targeted delivery of imaging agents (radionuclides, gold- or magnetic nanoparticles) and drugs that can remediate the inflammatory disease outcome and be translated readily into the clinic.