Our research focuses on the development and functional specialization of tissue-resident macrophages. We focus on the interactions between the macrophages and their tissue-specific niche.
Our research focuses on the development and functional specialization of tissue-resident macrophages. We focus on the interactions between the macrophages and their tissue-specific niche and study the mutually beneficial cell-cell circuits between these cells. We take a modular view of tissues that integrates the resident macrophage as an essential component of each individual module. We focus most of our work on liver myeloid cells. We are particularly interested in: (i) identifying the transcription factors that imprint the liver-specific identities in each of the liver module partners, (ii) identifying the cell-cell circuits within the liver module and (iii) unraveling the role of each module partner in the maintenance of liver homeostasis and (iv) understanding what cell-cell circuits instruct liver regeneration and the formation of novel liver modules.
To address these questions we combine unique in vivo transgenic mouse models with state-of-the-art in silico approaches in close collaboration with the Data Mining and Modelling for Biomedicine group (Dambi) headed by Yvan Saeys. We use 25-color flow cytometry, 8-color confocal microscopy, electron microscopy and intravital microscopy and perform single-cell- and spatial transcriptomics.
Integration of resident macrophages within tissue modules. Here we compare isolated villages to the putative lung alveolar modules and liver sinusoidal modules. The macrophage is compared to a central bakery (left) or pizzeria (right) that is integrated within the village and that requires complex interactions to function: electricity (trophic factors, blue) keeps the shop running, orders are compared to tissue-specific instructive signals (purple) that induce the master chef/transcription factors (red) to control their cooking/intracellular machinery (orange) to process ingredients (input, green) into the processed end-product (output, brown). See Guilliams et al. Immunity 2020. Art work by Sigrid Knemeyer and Matt Crotts from SciStories, LLC.
- We are partner of the Liver Human Cell Atlas Consortium. This is funded by the Chan Zuckerberg Initiative (CZI). This an international team with Sonya MacParland, Gary Bader, Alan Mullen, Shalev Itzkovitz, Neil Henderson, Ludovic Vallier, Dominic Grün, Sarah Teichmann, Ramnik Xavier and Aviv Regev. My team will profile liver immune cells.
We have ongoing collaborations with the teams of Yvan Saeys, Charlotte Scott, Bart Lambrecht & Hamida Hammad, Geert Van Loo and Dirk Elewaut within the Center for Inflammation Research.
- Ontogeny of dendritic cells and macrophages
- Correct identification of dendritic cell and macrophage subsets across species and tissues in steady state and in various inflammatory settings
- Construction of dendritic cell- and macrophage-specific knock-in mice for the study of the functional specialization of these cells in vivo.
Technology Transfer Potential
- Novel mouse models for the study of Kupffer Cells and Alveolar macrophages in vivo.
- Study of the role of macrophage subsets in the regulation of immune responses.
This research is part of the VIB Grand Challenges Program.