Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.
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DOI:
10.1242/dev.194563
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发表时间:
2021-02-03
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Riley PR
Riley PR
中科院分区:
其他
文献类型:
--
作者:
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;Riley PR

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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. Tissue-resident macrophages are indispensable mediators of lymphatic vessel formation during heart development, and function to remodel the vascular plexus.
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