Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Feb 9:8:104.
doi: 10.3389/fimmu.2017.00104. eCollection 2017.

microRNAs in the Lymphatic Endothelium: Master Regulators of Lineage Plasticity and Inflammation

Daniel Yee  1 , Mark C Coles  1 , Dimitris Lagos  1
Affiliations
Review

microRNAs in the Lymphatic Endothelium: Master Regulators of Lineage Plasticity and Inflammation

Daniel Yee et al. Front Immunol. .

Abstract

microRNAs (miRNAs) are highly conserved, small non-coding RNAs that regulate gene expression at the posttranscriptional level. They have crucial roles in organismal development, homeostasis, and cellular responses to pathological stress. The lymphatic system is a large vascular network that actively regulates the immune response through antigen trafficking, cytokine secretion, and inducing peripheral tolerance. Here, we review the role of miRNAs in the lymphatic endothelium with a particular focus on their role in lymphatic endothelial cell (LEC) plasticity, inflammation, and regulatory function. We highlight the lineage plasticity of LECs during inflammation and the importance of understanding the regulatory role of miRNAs in these processes. We propose that targeting miRNA expression in lymphatic endothelium can be a novel strategy in treating human pathologies associated with lymphatic dysfunction.

Keywords: inflammation; lineage plasticity; lymphangiogenesis; lymphatic endothelial cells; microRNA.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The effect of inflammation on the microRNAs (miRNA) landscape of lymphatic endothelial cells (LECs). (A) Under homeostatic conditions, miRNAs, including miR-126, miR-21, and miR-132, contribute to normal LEC function. Lymphatic identity is maintained through suppression of the blood endothelial cell (BEC)-enriched miRNAs miR-31 and miR-181a, which can repress LEC-specific genes, including the master LEC fate regulator PROX1 and the receptor tyrosine kinase vascular endothelial growth factor receptor-3 (VEGFR-3). (B) During inflammation, a set of immunologically active miRNAs (miR-155, miR-132, miR-146a) are induced and shape LEC immune responses. In addition, LEC-specific genes are downregulated and miRNAs, including miR-9, miR-1236, and miR-K12-11, a viral ortholog of miR-155, contribute to the loss of LEC identity. It is likely that other miRNAs may modulate immune gene expression and lineage plasticity in LECs.
See this image and copyright information in PMC

References

    1. Swartz MA. The physiology of the lymphatic system. Adv Drug Deliv Rev (2001) 50(1–2):3–20.10.1016/S0169-409X(01)00150-8 - DOI - PubMed
    1. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol (2010) 10(2):111–22.10.1038/nri2708 - DOI - PubMed
    1. Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol (2013) 14(8):475–88.10.1038/nrm3611 - DOI - PubMed
    1. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol (2014) 15(8):509–24.10.1038/nrm3838 - DOI - PubMed
    1. Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet (2011) 12(2):99–110.10.1038/nrg2936 - DOI - PubMed