Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/13308
Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.
Cahill, Thomas J | Sun, Xin | Ravaud, Christophe | Villa del Campo, Cristina CNIC | Klaourakis, Konstantinos | Lupu, Irina-Elena | Lord, Allegra M | Browne, Cathy | Jacobsen, Sten Eirik W | Greaves, David R | Jackson, David G | Cowley, Sally A | James, William | Choudhury, Robin P | Vieira, Joaquim Miguel | Riley, Paul R
Development. 2021; 148(3):dev.194563
Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1 + myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.
Lymphatic Vessels | Animals | CX3C Chemokine Receptor 1 | Cell Adhesion | Cell Line | Endothelial Cells | Gene Expression Regulation, Developmental | Gene Knock-In Techniques | Heart | Humans | Inflammation | Lymphangiogenesis | Macrophages | Mice | Mice, Inbred C57BL | Organogenesis | Receptors, Granulocyte-Macrophage Colony-Stimulating Factor | Yolk Sac