Lymphatic endothelial cells actively shape immune responses in the lungs

Lymphatic vessels maintain fluid balance and immune protection by transporting fluid, solutes and cells from tissue interstitial spaces to lymph nodes. The lymphatic endothelial cells that form lymphatics differentiate throughout the body to fulfil organ-specific roles. In the lungs, specialised pulmonary lymphatic endothelial cells mount active responses that are implicated in limiting acute inflammation, modulating adaptive immunity and influencing tissue remodelling. In this review, we outline the experimental evidence for how pulmonary lymphatic endothelial cells control inflammation and immune responses, through mechanisms including PAR1-mediated permeabilisation of lymphatic junctions, LIFR-mediated upregulation of CCL21 chemokine release and a variety of effects of VEGFR-3 activation. We then consider important directions for future research needed to achieve therapeutic harnessing of pulmonary lymphatic functions.