1. Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.
- Author
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Cahill TJ, Sun X, Ravaud C, Villa Del Campo C, Klaourakis K, Lupu IE, Lord AM, Browne C, Jacobsen SEW, Greaves DR, Jackson DG, Cowley SA, James W, Choudhury RP, Vieira JM, and Riley PR
- Subjects
- Animals, CX3C Chemokine Receptor 1 genetics, Cell Adhesion, Cell Line, Endothelial Cells, Gene Expression Regulation, Developmental, Gene Knock-In Techniques, Humans, Inflammation, Lymphangiogenesis, Macrophages immunology, Mice, Mice, Inbred C57BL, Organogenesis genetics, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor genetics, Yolk Sac, Heart growth & development, Lymphatic Vessels, Macrophages metabolism
- Abstract
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., Competing Interests: Competing interestsP.R.R. is co-founder and equity holder in OxStem Cardio, an Oxford University spin-out that seeks to exploit therapeutic strategies stimulating endogenous repair in cardiovascular regenerative medicine., (© 2021. Published by The Company of Biologists Ltd.)- Published
- 2021
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