Blood vessels instruct immune cells: an essential dialogue to preserve lung health
The lungs are in constant contact with our environment, exposed to the air we breathe. To function properly, they rely on a complex local immune system. Researchers from the GIGA Institute (University of Liège) have unveiled an unexpected cellular dialogue between blood vessel endothelial cells and interstitial macrophages, a specialized population of immune cells in the lung.
Published in Science Immunology and supported by the WEL Research Institute, the European Research Council (ERC) and the Baillet Latour Fund, this study demonstrates that the molecule TGFβ1, produced by endothelial cells, is essential for directing circulating monocytes to differentiate into mature interstitial macrophages that support lung structure.
“What we discovered is a true educational program set up by blood vessels to transform circulating immune cells into guardians of lung tissue,” explains Prof. Thomas Marichal, co-lead author of the study alongside Dr. Qiang Bai.
Using cutting-edge technologies—including single-cell transcriptomics, multiplex imaging, and genetically engineered mouse models, all available at the GIGA technological platforms—the team showed that the absence of the TGFβ receptor in monocytes prevents them from becoming functional interstitial macrophages. As a result, immature cells accumulate around blood vessels, ultimately leading to structural and functional alterations typical of premature lung aging: alveolar enlargement, loss of elasticity, increased collagen deposition, and reduced levels of anti-inflammatory factors.
“By disrupting this vascular-immune cell dialogue, we observe young lungs displaying features of aged lungs,” adds Wen Peng, first author of the study.
This discovery highlights the importance of so-called "trophic" signals delivered locally by endothelial cells to instruct the fate and function of resident macrophages. Much like what has been described in the brain and gut, this work reinforces the idea that each tissue speaks its own molecular language to shape its specialized immune cells.
In the long term, these findings could pave the way for therapeutic strategies aimed at restoring or boosting interstitial macrophage populations in various pathological contexts—chronic lung diseases, aging, fibrosis, or recovery from severe respiratory infections.
Reference
Endothelial-driven TGFβ signaling supports lung interstitial macrophage development from monocytes.
Wen Peng 1,2, Domien Vanneste 1,2, David Bejarano 3, Joan Abinet 1,2, Margot Meunier 1,2, Coraline Radermecker 1,2, Fabienne Perin 4, Didier Cataldo 4, Fabrice Bureau 2,5, Andreas Schlitzer 3, Qiang Bai 1,6,* & Thomas Marichal 1,2,7,*
Affiliations :
1 Laboratory of Immunophysiology, GIGA Institute, University of Liège; Liège, Belgium
2 Faculty of Veterinary Medicine, University of Liège; Liège, Belgium
3 Quantitative Systems Biology, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
4 Laboratory of Tumor and Development Biology, GIGA Institute, University of Liège; Liège, Belgium
5 Laboratory of Cellular and Molecular Immunology, GIGA Institute, University of Liège; Liège, Belgium
6 PhyMedExp INSERM 1046, University of Montpellier, Montpellier, France
7 Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute; Wavre, Belgium
* These authors contributed equally to this work and are co–last authors.
*Corresponding authors: t.marichal@uliege.be; qiang.bai@inserm.fr
Sci. Immunol. 9, eado1227 (2024)
DOI: 10.1126/sciimmunol.adr4977
Fundings
WELBIO, ERC, Fund for Scientific Research - FNRS, Fonds Baillet Latour
Contact
WEL Research Institute Investigator
GIGA – Laboratory of Immunophysiology
