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oai:repisalud.isciii.es:20.500.12105/133082024-09-27T09:07:28Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Cahill, Thomas J author Sun, Xin author Ravaud, Christophe author Villa del Campo, Cristina author Klaourakis, Konstantinos author Lupu, Irina-Elena author Lord, Allegra M author Browne, Cathy author Jacobsen, Sten Eirik W author Greaves, David R author Jackson, David G author Cowley, Sally A author James, William author Choudhury, Robin P author Vieira, Joaquim Miguel author Riley, Paul R author 2021-01 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. Development. 2021; 148(3):dev.194563 0950-1991 http://hdl.handle.net/20.500.12105/13308 33462113 10.1242/dev.194563 1477-9129 Development (Cambridge, England) Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.