Abstract
The lymphatic system is a vascular system comprising modified lymphatic endothelial cells, lymph nodes and other lymphoid organs. The system has diverse, but critical functions in both physiology and pathology, and forms an interface between the blood vascular and immune system. It is increasingly evident that remodelling of the lymphatic system occurs alongside remodelling of the blood microvascular system, which is now considered a hallmark of most pathological conditions as well as being critical for normal development. Much attention has focussed on how the blood endothelium undergoes phenotypic switching in development and disease, resulting in over two decades of research to probe the mechanisms underlying the resulting heterogeneity. The lymphatic system has received less attention, and consequently there are fewer descriptions of functional and molecular heterogeneity, but differential transcription factor activity is likely an important control mechanism. Here we introduce and discuss significant transcription factors of relevance to coordinating cellular responses during lymphatic remodelling as the lymphatic endothelium dynamically changes from quiescence to actively remodelling.
Highlights
Reviewed by: Erik Josef Behringer, Loma Linda University, United States Walter Emerson Cromer, Texas A&M Health Science Center, United States
Other transcription factors identified as shared between mouse and human LECs include with heterogenous expression across the lymph node include KLF4 (Takeda et al, 2019; Xiang et al, 2020), which has been demonstrated to be a key regulator of the components of flow-induced LEC proliferation (Choi et al, 2017) and RELB (Takeda et al, 2019; Xiang et al, 2020), a member of the nuclear factor-κB (NF-κB) family (Yang et al, 2019) known to play a key role in the development and function of lymphatic vessels mediated by LECs (Liang et al, 2019)
Understanding the lymphatic endothelium will be as important as the blood endothelium as the site of major disease in the coming years
Summary
The lymphatic vascular system comprises a hierarchical system of lymphatic capillaries, that drain into higher calibre collecting vessels that return protein rich lymph (generated from interstitial fluid) and trafficking cells (e.g., lymphocytes and myeloid) back into the venous circulation. As the lymphatic system evolved it allowed higher order eukaryotes to have a regulated fluid balance system. (Lymphatic vessels are found in reptiles, amphibians, birds and mammals) (Adams and Alitalo, 2007). Extravasated water, solutes and cells are forced out the vascular system at higher pressure, resulting in fluid leakage from the permeable capillaries into the interstitium.
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