Mapping of human fibroblasts´ capacities to shape the macrophage pool in human tissue

The biological importance of fibroblasts is undisputed.

However, in depth fibroblast characterization on protein level in situ and ex vivo, as well their functional relationship with immune cells, such as macrophages, in microanatomical niches do not exist today.

Macrophages are found in all tissues, and are important for tissue homeostasis, as well as in controlling infection and inflammation.

We hypothesize that the contrasting functions of macrophages in tissue might be linked to tissue and context dependent modulation through fibroblasts.

Our preliminary data indicate that (PDGFRA+CD142-) fibroblasts co-localize with monocytes/macrophages in human inflamed and non-inflamed intestine.

Through access to organ donor tissue and well-characterized patient samples, as well as cutting edge single cells RNA sequencing, multiparameter flow cytometry, and novel ultra-high content imaging technologies combined with advanced in-house developed cell culture-systems, we will (1) investigate transcriptional fibroblast heterogeneity across and within human tissue (2) validate transcriptional data at protein and cellular levels, and (3) investigate the conditions and prerequisites for fibroblasts shaping the macrophage pool.

The proposed research has the potential to provide new mechanistical insights into tissue homeostasis, inflammation, and resolution, as well as into fibroblast functions which can be explored in novel therapeutic approaches targeting fibroblasts in disease.