Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation
OPEN ACCESS
Author / Producer
Date
2016
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Rights / License
Abstract
Vascular endothelial growth factor-C (VEGF-C)-induced lymphangiogenesis and increased tissue drainage have been reported to inhibit acute and chronic inflammation, and an activated lymphatic endothelium might mediate peripheral tolerance. Using transgenic mice overexpressing VEGF-C in the skin, we found that under inflammatory conditions, VEGF-C-mediated expansion of the cutaneous lymphatic network establishes an immune-inhibitory microenvironment characterised by increased regulatory T (Treg) cells, immature CD11c+CD11b+ dendritic cells (DCs) and CD8+ cells exhibiting decreased effector function. Strikingly, lymphatic endothelial cell (LEC)-conditioned media (CM) potently suppress DC maturation with reduced expression of MHCII, CD40, and IL-6, and increased IL-10 and CCL2 expression. We identify an imbalance in prostaglandin synthase expression after LEC activation, favoring anti-inflammatory prostacyclin synthesis. Importantly, blockade of LEC prostaglandin synthesis partially restores DC maturity. LECs also produce TGF-ß1, contributing to the immune-inhibitory microenvironment. This study identifies novel mechanisms by which the lymphatic endothelium modulates cellular immune responses to limit inflammation.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
7 (26)
Pages / Article No.
39421 - 39435
Publisher
Impact Journals
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
inflammation; lymphangiogenesis; VEGF-C; Immunology and Microbiology Section; Immune response; Immunity
Organisational unit
03683 - Detmar, Michael (emeritus) / Detmar, Michael (emeritus)
Notes
Funding
147087 - Molecular mechanisms of angiogenesis and lymphangiogenesis in inflammation and cancer progression (SNF)